The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia.

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

The effect of silicone oil presence time on macular and choroidal thickness with macula-off rhegmatogenous retinal detachment.

OBJECTIVE: To investigate the effects of silicone oil (SiO) on macular thickness (MT) and subfoveal choroidal thickness (SFCT) in patients with macula-off rhegmatogenous retinal detachment (RRD) undergoing pars plana vitrectomy (PPV). MATERIAL AND METHODS: In this prospective study, 70 eyes of 70 patients who received SiO tamponade for the treatment of macula-off RRD were treated with PPV and a 5000-cSt SiO endotamponade followed by subsequent SiO removal. MT and SFCT were measured 1 day before and 3 months after SiO removal using spectral-domain optical tomography (SD-OCT) and enhanced depth imaging optical tomography (EDI-OCT). The patients were divided into 3 groups according to the length of time that the SiO was present: group 1 (3-6 months), group 2 (6-9 months), and group 3 (9-18 months). RESULTS: A total of 70 eyes of 70 patients with a mean age of 57.22±9.83 years (range: 30 years to 75 years) were included in the SiO (5000-cSt) study. SiO was extracted after a mean duration of 8.67±5.33 months (range, 3-18 months) after PPV. In the 1st group, BCVA increased from 1.83±0.32 log MAR before PPV to 0.85±0.41 log MAR at 3 months after silicone removal (P<0.001). In the 2nd group, BCVA increased from 1.76±0.38 log MAR before PPV to 0.86±0.48 log MAR at 3 months after silicone removal (P<0.001). In the 3rd group, BCVA increased from 1.89±0.28 log MAR before PPV to 1.08±0.63 log MAR at 3 months after SiO removal (P=0.001). There was no statistically significant change in MT in the difference values of each group. As the length of SiO presence in the eye increased, significant thinning was observed on measurement of SFCT. Differences in the SFCT values were -14.91µm, -18.76µm, and -51.50µm in groups 1, 2, and 3 respectively (P=0.004). CONCLUSIONS: A significant decrease in macular and choroidal thicknesses after SiO removal was observed. Presence of SiO endotamponade for 9 months was associated with subfoveal choroidal thinning and decreased final visual acuity in eyes undergoing RRD surgery. SD-OCT and EDI-OCT may be recommended for the treatment and follow-up of patients with complications caused by the use of SiO tamponade.

Long-term exposure to a continuous 900 MHz electromagnetic field disrupts cerebellar morphology in young adult male rats.

The pathological effects of exposure to an electromagnetic field (EMF) during childhood and adolescence may be greater than those from exposure during adulthood. We investigated possible pathological changes in the cerebellum of adolescent rats exposed to 900 MHz EMF daily for 25 days. We used three groups of six 21-day-old male rats as follows: unexposed control group (Non-EG), sham-exposed group (Sham-EG) and an EMF-exposed group (EMF-EG). EMF-EG rats were exposed to EMF in an EMF cage for 1 h daily from postnatal days 21 through 46. Sham-EG rats were placed in the EMF cage for 1 h daily, but were not subjected to EMF. No procedures were performed on the Non-EG rats. The cerebellums of all animals were removed on postnatal day 47, sectioned and stained with cresyl violet for histopathological and stereological analyses. We found significantly fewer Purkinje cells in the EMF-EG group than in the Non-EG and Sham-EG groups. Histopathological evaluation revealed alteration of normal Purkinje cell arrangement and pathological changes including intense staining of neuron cytoplasm in the EMF-EG group. We found that exposure to continuous 900 MHz EMF for 1 h/day during adolescence can disrupt cerebellar morphology and reduce the number of Purkinje cells in adolescent rats.

Depression and socio-economical burden are more common in primary caregivers of patients who are not aware of their cancer: TURQUOISE Study by the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

In this study, we aimed to determine the personal, social and economic burden and the frequency of depression, as well as in caregivers of cancer patients who are being treated with chemotherapy in Turkey. The study is designed as a cross-sectional survey study using a 5-point Likert-type response scale, and the last part of the questionnaire includes the Beck Depression Inventory. The depression rate was found to be 64% (n = 476) among all subjects (n = 968), with 91% of those with depression demonstrating signs of mild depression. In this study, a significant difference was found between the presence of depression and age (young), sex (female), educational level (high), economic status (low), financial loss during treatment, patient's lack of knowledge about his/her diagnosis, metastatic disease and short survival time. In addition, 64% of all subjects had concerns of getting cancer, and 44% of all subjects had feelings of anger/rage against other people. In a multivariate regression analysis, the patient's lack of knowledge of the diagnosis was the independent risk factor. In conclusion, depression incidence and burden rate increased among cancer caregivers, and care burden was highly associated with depression. Accordingly, approaches to reducing the psycho-social effects of cancer should focus intensively on both the patients and their caregivers in Turkey.

Deconstructive and Reconstructive Techniques in Treatment of Vertebrobasilar Dissecting Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Various endovascular techniques have been applied to the treatment of vertebrobasilar dissecting aneurysms, including parent artery preservation with coiling, stent placement or flow diverter placement, and trapping and proximal occlusion. We performed a systematic review and meta-analysis to study clinical and angiographic outcomes of patients undergoing endovascular treatment of vertebrobasilar dissecting aneurysms. MATERIALS AND METHODS: We performed a comprehensive literature search for studies on the endovascular treatment of vertebrobasilar dissecting aneurysms. From each study we abstracted the following data: immediate occlusion, long-term occlusion, long-term good neurologic outcome, perioperative morbidity, perioperative mortality, rebleed (ruptured only), recurrence, and retreatment. We performed subgroup analyses of patients undergoing deconstructive-versus-reconstructive techniques. Meta-analysis was performed by using a random effects model. RESULTS: Seventeen studies with 478 patients were included in this analysis. Sixteen studies had at least 6 months of clinical/angiographic follow-up. Endovascular treatment was associated with high rates of long-term occlusion (87.0%; 95% CI, 74.0%-94.0%) and low recurrence (7.0%; 95% CI, 5.0%-10.0%) and retreatment rates (3.0%; 95% CI, 2.0%-6.0%). Long-term good neurologic outcome was 84.0% (95% CI, 65.0%-94.0%). Deconstructive techniques were associated with higher rates of long-term complete occlusion compared with reconstructive techniques (88.0%; 95% CI, 35.0%-99.0% versus 81.0%; 95% CI, 64.0%-91.0%; P < .0001). Deconstructive and reconstructive techniques were both associated with high rates of good neurologic outcome (86.0%; 95% CI, 68.0%-95.0% versus 92.0%; 95% CI, 86.0%-95.0%; P = .10). CONCLUSIONS: Endovascular treatment of vertebrobasilar dissecting aneurysms is associated with high rates of complete occlusion and good long-term neurologic outcomes. Deconstructive techniques are associated with higher occlusion rates. There was no statistical difference in neurologic outcomes between groups, possibly due to low power.

Duration of anti-HER2 blockage therapy may improve survival in HER2 positive metastatic breast carcinoma patients.

PURPOSE: The duration of anti-HER2 blockage therapy in metastatic breast cancer patients is still unclear. We aimed to evaluate the effect of the anti-HER2 blockage therapy duration and other factors on survival in HER2 positive metastatic breast carcinoma (MBC) patients. METHODS: The medical records of 193 HER2 positive MBC patients, who did not have the opportunity to receive adjuvant trastuzumab therapy but had received trastuzumab in the metastatic setting were retrospectively evaluated. RESULTS: The median age at diagnosis was 45.0 years (range 21-83). Ninety-two (47.7%) patients received palliative trastuzumab < 6 months median, whereas 101 patients received trastuzumab ≥ 6 months median. The median number of trastuzumab cycles was 8 (range 1-51). Median survival after breast cancer recurrence was 31.0 months (range 24.3-37.7). The duration of trastuzumab therapy had a significant impact on the prognosis of recurrent breast cancer (22.0 vs 49.0 months, for ≤ 6 months of treatment duration, respectively; p<0.0001). Survival after breast cancer recurrence for the patients who received lapatinib plus capecitabine vs those who did not was significantly different (59 patients, p=0.005). Moreover, there was a statistically significant relationship between prolonged lapatinib plus capecitabine combination therapy and improved survival after disease recurrence (p=0.022). In the multivariate Cox regression analysis, treatment with trastuzumab > 6 months (p=0.003) was the only independent prognostic factor for survival after breast cancer recurrence. CONCLUSION: The duration of anti-HER2 blockage therapies, especially with trastuzumab, seems to improve survival of HER2-positive metastatic breast cancer patients who were not previously treated with adjuvant trastuzumab, regardless of other therapies.

Endocrine therapy alone vs. chemotherapy plus endocrine therapies for the treatment of elderly patients with endocrine-responsive and node positive breast cancer: a retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology).

PURPOSE: The extra benefit of adding chemotherapy to effective endocrine therapy (ET) has not been clearly or consistently identified in patients older than 70 years with estrogen receptor (ER) positive and node positive breast cancer. The aim of this study was to evaluate the efficacy of adjuvant ET vs. chemotherapy plus endocrine therapies (Chemo/ET) in such patients. METHODS: In this retrospective multicenter study 191 patients ≥ 70 years with operated hormone receptor breast cancer, who were administered adjuvant ET or Chemo/ET were assessed. RESULTS: The median patient follow-up time was 29.0 months (range 1-252). Therefore disease free survival (DFS) and overall survival (OS) analysis was limited, due to the rather short median follow-up, and only 30-month cumulative percentages are reported herein. The 30-month DFS rates were 50.0% in the ET arm and 49.0% in the Chemo/ET arm (p=0.79). The 30-month OS rates were 86% in the ET arm and 96.0% in the Chemo/ET arm (p=0.08). Cox proportional hazard model showed that only surgery was independent prognostic factor for survival (p=0.047), while tumor size showed a strong trend for statistical significance (p=0.051). CONCLUSION: The addition of chemotherapy to endocrine therapy in older patients has no significant impact on DFS and OS.

Does pantoprazole protect against reperfusion injury following myocardial ischemia in rats?

BACKGROUND: Myocardial ischemia is inadequate perfusion due to reduced blood flow. Sudden onset of reperfusion could result with damage to the myocytes that have not been affected during ischemia called ischemia reperfusion (I/R) injury. Extracellular accumulation of H+ ions resulting in tissue acidosis is one of the underlying mechanisms. Inhibition of myocardial H+/K+-ATPase, namely proton pump, may lead to intracellular acidification via decreasing the extracellular H+ transport. AIM: The aim of this study is to investigate the effects of a proton pump inhibitor pantoprazole in intact rat I/R models. MATERIALS AND METHODS: A total of 30 adult male Wistar albino rats weighing 200-300 g were studied. Rats were allocated into four groups: sham (n=6), ischemia (n=8), control (n=8), and pantoprazole (n=8). Left anterior descending coronary artery was occluded for 30 minutes and then reperfused for two hours. Pantoprazole was administered via jugular vein at the dose of 9 mg/kg starting from 30 minutes before ischemia, to the first 30 minutes of reperfusion. Haemodynamic parameters were recorded and serum CK-MB levels were measured. After reperfusion, heart was removed for the measurement of myocardial infarct size. Myocardial infarct area was measured using triphenyltetrazolium chloride (TTC) staining technique. Myocardial infarction size were expressed as the percentage of the total left ventricular weight. RESULTS: Compared with other groups, plasma concentrations of CK-MB at the end of ischemia and reperfusion and myocardial infarct size were significantly lower in pantoprazole group (p < 0.008). CONCLUSIONS: Pantoprazole preconditioning induces delayed cardioprotection in intact rat I/R model, which may be triggered via H+/K+-ATPase ion channels.

Comparison of four methods for the estimation of intracranial volume: a gold standard study.

Investigators can infer how much reduction in volume has occurred since brain volume was at its peak, by combining measures of brain volume with measures of intracranial volume (ICV). Several methodologies have been proposed to asses the ICV. However, we have not seen a gold-standard study evaluating the results of the methodologies for the assessment of ICV. In the present study, the actual intracranial volume of 20 dry skulls was measured using the water-filling method, using this as a gold standard. Anthropometry, cephalometry, point-counting, and planimetry techniques were applied to the same skulls to estimate the ICV. Anthropometric and cephalometric measurements were carried out directly on skulls and roentgenograms, respectively. Consecutive computed tomography sections at a thickness of 10 mm were used to estimate the ICV of the skulls by means of the point-counting and planimetry methods. The mean (+/-SD) of the actual ICV measured by the water-filling method was 1,262.0 +/- 160.4 cm(3) (1,389.5 +/- 96.5 cm(3) for males and 1,134.5 +/- 94.3 cm(3) for females, respectively). Our results showed that the estimated values obtained by all four methods differed from the actual volumes of the skulls (P < 0.05). The data obtained by anthropometry resulted in overestimation. However, cephalometry, point-counting, and planimetry methods produced underestimation. After calibration, there were no significant differences between the actual volumes and the results of the four methods (P > 0.05). While the anthropometric method is easy and quick to apply, its result may deviate from the actual values. The optimized stereological techniques of point-counting and planimetry methods may provide unbiased ICV results since they take the third dimension of the structures into account.

Therapeutic effects of intracarotid infusion of spermine/nitric oxide complex on cerebral vasospasm.

BACKGROUND: Vasospasm is one of the underlying causes of morbidity and mortality in subarachnoid haemorrhage (SAH). The therapeutic effects of intracarotid infusion of spermine/nitric oxide complex (SPER/NO) on cerebral vasospasm in an experimental model of SAH were investigated. METHOD: Twenty-four adult male New Zealand white rabbits (2.6-3.4 kg in weight) were randomly divided into four groups (n=6), as follows: (I) control group (without SAH and drug), (II) SAH alone group (with SAH, without drug), (III) SAH placebo group (with SAH and saline), and (IV) SAH-SPER/NO group (with SAH and SPER/NO). The fresh autologous non-heparinized blood was injected into the cisterna magna to induce a SAH, after 24 hour SAH, the substance (saline or SPER/NO) was delivered to animals. All rabbits were scarified at 48-hours of induced SAH. The basilar artery with surrounding tissue was removed from the cranium and processed for paraffin embedding. Histopathological and stereological examinations of the basilar artery were done. FINDINGS: In the SPER/NO treated group of rabbits, the histopathological changes were less severe than in the SAH-alone and SAH-placebo groups. Regarding the intracarotid pressure, there was a statistically significant difference between SAH-alone and SAH-SPER/NO groups and also between SAH-SPER/NO and control groups (p<0.05). The mean cross sectional area of basilar arteries was 0.26 mm(2) in the control, whereas in SAH alone, placebo and SAH-SPER/NO groups were 0.13, 0.15 and 0.20 mm(2), respectively. INTERPRETATION: It is well known that NO is a critical substance involved in cerebral vascular dynamics. Present results indicate that treatment of vasospasm with SPER/NO in SAH may be promising. However, further studies should be done on this substance to clarify its effect on vasospasm before using the drug in clinical situations.

Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-alpha and interleukin-1 beta concentrations on outcome of full term infants with hypoxic-ischaemic encephalopathy.

AIM: To determine the predictive value of plasma and cerebrospinal fluid (CSF) tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) concentrations on the outcome of hypoxic-ischaemic encephalopathy (HIE) in full term infants. METHODS: Thirty term infants with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life and stored until assay. Five infants died soon after hypoxic insult. Neurological examinations and Denver Developmental Screening Test (DDST) were performed at 12 months in the survivors. RESULTS: At the age of 12 months neurological examination and DDST showed that 11 infants were normal; 14 had abnormal neurological findings and/or an abnormal DDST result. Eleven normal infants were classified as group 1 and 19 infants (14 with abnormal neurological findings and/or an abnormal DDST and five who died) as group 2. CSF IL-1 beta and TNF-alpha concentrations in group 2 were significantly higher than those in group 1. Plasma IL-1 beta and TNF-alpha concentrations were not significantly different between the two groups. IL-1 beta, but not TNF-alpha concentrations, in group 2 were even higher than those in group 1, although non-survivors were excluded from group 2. When the patients were evaluated according to the stages of Sarnat, the difference in the three groups was again significant. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 beta and TNF-alpha concentrations than the patients whose samples were taken after 6 hours. CONCLUSIONS: Both cytokines probably contribute to the damage sustained by the central nervous system after hypoxic insult. IL-1 beta seems to be a better predictor of HIE than TNF-alpha.