Use of robotics in oncologic surgery is increasing; however, reports of safety and efficacy are from highly experienced surgeons and centers. We performed a population-based analysis to compare laparoscopic hysterectomy and robotic hysterectomy for endometrial cancer.
Patients and Methods
The Perspective database was used to identify women who underwent a minimally invasive hysterectomy for endometrial cancer from 2008 to 2010. Morbidity, mortality, and cost were evaluated using multivariable logistic and linear regression models.
We identified 2,464 women, including 1,027 (41.7%) who underwent laparoscopic hysterectomy and 1,437 (58.3%) who underwent robotic hysterectomy. Women treated at larger hospitals, nonteaching hospitals, and centers outside of the northeast were more likely to undergo a robotic hysterectomy procedure, whereas black women, those without insurance, and women in rural areas were less likely to undergo a robotic hysterectomy procedure (P < .05 for all). The overall complication rate was 9.8% for laparoscopic hysterectomy versus 8.1% for robotic hysterectomy (P = .13). The adjusted odds ratio (OR) for any morbidity for robotic hysterectomy was 0.76 (95% CI, 0.56 to 1.03). After adjusting for patient, surgeon, and hospital characteristics, there were no significant differences in the rates of intraoperative complications (OR, 0.68; 95% CI, 0.42 to 1.08), surgical site complications (OR, 1.49; 95% CI, 0.81 to 2.73), medical complications (OR, 0.64; 95% CI, 0.40 to 1.01), or prolonged hospitalization (OR, 0.85; 95% CI, 0.64 to 1.14) between the procedures. The mean cost for robotic hysterectomy was $10,618 versus $8,996 for laparoscopic hysterectomy (P < .001). In a multivariable model, robotic hysterectomy was significantly more costly ($1,291; 95% CI, $985 to $1,597).
Despite claims of decreased complications with robotic hysterectomy, we found similar morbidity but increased cost compared with laparoscopic hysterectomy. Comparative long-term efficacy data are needed to justify its widespread use.
To investigate the prognostic factors and effectiveness of postoperative radiotherapy alone for endometrial carcinoma.
Materials and Methods
Sixty four patients with stage I-III endometrial cancer (EC) treated with postoperative radiotherapy alone between January 1989 and December 2008 at the Keimyung University Dongsan Medical Center were chosen for the present study. Typically, total hysterectomy, salpingo-oophorectomy and lymphadenectomy were performed on the patient's pelvis. Total dose from 50.4 Gy to 63 Gy was irradiated at pelvis or extended field. Thirteen patients were treated with Co-60 or Ir-192 intracavitary radiotherapy. Follow-up periods were from 7 to 270 months, with a median of 56 months.
Five year overall survival (OS) rate was 58.7%, respectively. Five year disease-free survival (DFS) rate was 59.2%, respectively. In univariate analysis for OS and DFS, stage, menopausal age, type of operation, serosal invasion, and lymph node involvement were found to be statistically significant. Histologic type was marginally significant. In multivariate analysis for OS and DFS, stage, types of operation, histologic type were also found to be statistically significant. Treatment failure occurred in 14 patients. The main pattern of failure was found to be distant metastasis. Time to distant metastasis was from 3 to 86 months (median, 12 months). There were no grade 3 or 4 complications.
Stage, types of operation, and histologic type could be the predictive prognostic factors in patients. We contemplated postoperative radiation as effective and safe treatment method for EC. Additional treatment would be needed to reduce distant metastasis.
Endometrial neoplasm; Postoperative procedures; Adjuvant radiotherapy; Prognosis; Menopause
This randomized single-blinded, cross-over study was done to evaluate the influence of the size of tracheal tubes on air leaks around the cuffs.
In a benchtop model, the number of longitudinal folds on the cuffs was evaluated for different sizes of tracheal tubes. In an anesthetized patient study, thirty patients scheduled for elective surgery under general anesthesia were included. After induction of anesthesia, the trachea was intubated with two sizes of tracheal tubes in a random sequence: in men, internal diameter of 7.5 mm and 8.0 mm; in women, internal diameter of 7.0 mm and 7.5 mm. After tracheal intubation with each tube, air leak pressures were evaluated at intracuff pressures of 20, 25 and 30 cmH2O by auscultation. To calculate the tracheal tube resistance (R), an inspiratory pause of 20% was applied and the resulting peak airway pressure (Ppeak), plateau pressure (Ppl) and mean expiratory tidal volume (Flow) were inserted in the formula R = (Ppeak - Ppl)/Flow.
More longitudinal folds of the tracheal tube cuffs occurred in larger sized tubes compared to the smaller ones in a benchtop model. Air leakage was significantly less for the smaller tracheal tubes than for the larger ones for each gender at intracuff pressures of 20, 25 and 30 cmH2O. Tracheal tube resistances were not significantly altered by the size of tracheal tube.
The use of a smaller tracheal tube within an acceptable size can reduce air leakage around the cuff without significantly changing the tracheal tube resistance.
Anesthesia; Intratracheal; Intubation
Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes patients. Moderate hypoglycemia is not life-threatening, but if experienced recurrently it may present several clinical complications. Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. We therefore hypothesized that pyruvate may be able to improve the outcome in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose alone. In an effort to mimic juvenile type 1 diabetes the experiments were conducted in one-month-old young rats that were rendered diabetic by streptozotocin (STZ, 50mg/kg, i.p.) injection. One week after STZ injection, rats were subjected to moderate hypoglycemia by insulin injection (10U/kg, i.p.) without anesthesia for five consecutive days. Pyruvate (500mg/kg) was given by intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia, neuronal death, oxidative stress, microglial activation and GSH concentrations in the cerebral cortex were analyzed. Sparse neuronal death was observed in the cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss in the cortex after R/M hypoglycemia were all reduced by pyruvate injection. These findings suggest that when delivered alongside glucose, pyruvate may significantly improve the outcome after R/M hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.
The role of genetic polymorphisms of tumor necrosis factor-alpha (TNF-α) for lung cancer development was evaluated.
Genotypes of the TNF-α polymorphisms, -1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, were determined in 616 lung cancer cases and 616 lung cancer-free controls.
After adjusting for body mass index and smoking, each TNF-α genotype or haplotype composed of five TNF-α single nucleotide polymorphisms did not show an association with lung cancer risk (p>0.05). The statistical power was found to be 88.4%, 89.3%, 93.3%, 69.7%, and 93.9% for 1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, respectively. Furthermore, the effects of each SNP or haplotype on lung cancer risk were not found to be different according to the cell type of lung cancer (p>0.05). In the repeated analysis with only subjects without other diseases related to inflammation, there was also no association between polymorphisms or haplotypes of the TNF-α gene and lung cancer risk (p>0.05).
This study found no association between common variants of the TNF-α gene and lung cancer risk.
Lung cancer risk; Polymorphism; Tumor necrosis factor-alpha
Olfactory sensitivity exhibits daily fluctuations. Several studies have suggested that the olfactory system in insects is modulated by both biogenic amines and neuropeptides. However, molecular and neural mechanisms underlying olfactory modulation in the periphery remain unclear since neuronal circuits regulating olfactory sensitivity have not been identified. Here, we investigated the structure and function of these signaling pathways in the peripheral olfactory system of the American cockroach, Periplaneta americana, utilizing in situ hybridization, qRT-PCR, and electrophysiological approaches. We showed that tachykinin was co-localized with the octopamine receptor in antennal neurons located near the antennal nerves. In addition, the tachykinin receptor was found to be expressed in most of the olfactory receptor neurons in antennae. Functionally, the effects of direct injection of tachykinin peptides, dsRNAs of tachykinin, tachykinin receptors, and octopamine receptors provided further support for the view that both octopamine and tachykinin modulate olfactory sensitivity. Taken together, these findings demonstrated that octopamine and tachykinin in antennal neurons are olfactory regulators in the periphery. We propose here the hypothesis that octopamine released from neurons in the brain regulates the release of tachykinin from the octopamine receptor neurons in antennae, which in turn modulates the olfactory sensitivity of olfactory receptor neurons, which house tachykinin receptors.
Many studies have shown a consistent association between ambient air pollution and an increase in death due to cardiovascular causes. An increase in blood pressure is a common risk factor for a variety of cardiovascular diseases. However, the association between air pollution and blood pressure has not been evaluated extensively.
In this cross‐sectional study, we measured blood pressure in 10 459 subjects who had a health examination from 2001 to 2003, and calculated individual's exposure to ambient levels of air pollutants. To evaluate the relationship between exposure to air pollutants and blood pressure with respect to season, we performed a multiple regression analysis, separately, according to season, controlling for individual characteristics and meteorological variables.
In the warm‐weather season (July–September), particulate air pollutant of <10 μm (PM10) and nitrogen dioxide (NO2) concentrations were significantly associated with measures of blood pressure. During cold weather (October–December), blood pressure was significantly associated with sulphur dioxide (SO2) and ozone (O3) concentrations. The significant association between PM10 or NO2 and blood pressure disappeared during the cold‐weather season.
We found a seasonal variation for the association between ambient air‐pollutant concentrations and blood pressure.
Hypoglycemia-induced brain injury is a common and serious complication of intensive insulin therapy experienced by Type 1 diabetic patients. We previously reported that hypoglycemic neuronal death is triggered by glucose reperfusion after hypoglycemia rather than as a simple result of glucose deprivation. However, the precise mechanism of neuronal death initiated by glucose reperfusion is still unclear. Autophagy is a self-degradation process that acts through a lysosome-mediated trafficking pathway to degrade and recycle intracellular components, thereby regulating metabolism and energy production. Recent studies suggest that autophagic and lysosomal dysfunction leads to abnormal protein degradation and deposition that may contribute to neuronal death. Here, we focused on the relationship between autophagy and lysosomal dysfunction in hypoglycemia-induced neuronal death. In neuronal cells, glucose reperfusion after glucose deprivation resulted in inhibition of autophagy, which may promote cell death. This cell death was accompanied with activation of caspase3 and the lysosomal proteases cathepsin B and D, which indicated impairment of autophagic flux. Taken together, these results suggest that interplay of autophagy, caspase3 activation and lysosomal proteases serve as a basis for neuronal death after hypoglycemia. Thus, we provide the molecular mechanism of neuronal death by glucose reperfusion and suggest some clues for therapeutic strategies to prevent hypoglycemia-induced neuronal death.
Primary mucosa-associated lymphoid tissue (MALT) lymphoma arising in the common bile duct (CBD) is extremely rare. In our case of MALT lymphoma, CT and MRI showed long, segmental, irregular wall thickening of the CBD and minimal dilatation of the upstream bile duct. A preoperative diagnosis of cholangiocarcinoma was made, but histologic evaluation confirmed MALT lymphoma of the CBD. We herein present a rare case of MALT lymphoma of the CBD with CT and MRI findings.
Mucosa-associated lymphoid tissue lymphomas; Common bile duct; CT; MRI
Insulin resistance (IR) is believed to be the underlying mechanism of metabolic syndrome and type 2 diabetes mellitus (DM). Recently, a few studies have demonstrated that phthalates could cause oxidative stress which would contribute to the development of IR. Therefore, we evaluated whether exposure to phthalates affects IR, and oxidative stress is involved in the phthalates-IR pathway.
We recruited 560 elderly participants, and obtained blood and urine samples during repeated medical examinations. For the determination of phthalate exposure, we measured urinary levels of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) as metabolites of diethylhexyl phthalates (DEHP), and mono-n-butyl phthalate (MnBP) as a metabolite of di-butyl phthalate (DBP). Malondialdehyde (MDA), an oxidative stress biomarker, was also measured in urine samples. We measured serum levels of fasting glucose and insulin, and derived the homeostatic model assessment (HOMA) index to assess IR. A mixed-effect model and penalized regression spline were used to estimate the associations among phthalate metabolites, MDA, and IR.
The molar sum of MEHHP and MEOHP (∑DEHP) were significantly associated with HOMA (β = 0.26, P = 0.040), and the association was apparent among participants with a history of DM (β = 0.88, P = 0.037) and among females (β = 0.30, P = 0.022). However, the relation between MnBP and HOMA was not found. When we evaluated whether oxidative stress is involved in increases of HOMA by ∑DEHP, MDA levels were significantly associated with increases of ∑DEHP (β = 0.11, P<0.001) and HOMA (β = 0.49, P = 0.049).
Our study results suggest that exposure to DEHP in the elderly population increases IR, which is related with oxidative stress, and that participants with a history of DM and females are more susceptible to DEHP exposure.
Background and Objectives
It was demonstrated that the fractional flow reserve (FFR) with partial balloon obstruction may have implications for assessing viable myocardium. In a different way, the index of microcirculatory resistance (IMR) was introduced as a useful indicator for assessing microvascular function. We evaluated the relationship between the FFR0.8 and the IMR.
Subjects and Methods
We studied 48 consecutive patients who had undergone coronary intervention for acute myocardial infarction (AMI). After revascularization using stent(s), an undersized short balloon was positioned inside the stent and inflated to create a specific normalized pressure drop of FFR (distal coronary/aortic pressure=0.80) at rest. The FFR0.8 was obtained during hyperemia with the fixed state balloon-induced partial obstruction. IMR was measured by three injections of saline. The association between the FFR0.8 and the IMR was investigated.
The mean age of the patients was 60±12 years and 36 (75%) overall presented with ST-segment elevation myocardial infarction. The mean FFR0.8 was 0.68±0.06. A statistically significant correlation between the FFR0.8 and the log-transformed IMRtrue (LnIMRtrue) was found through a multivariable linear regression analysis (β=0.056, p<0.001). Both the FFR0.8 and the LnIMRtrue had a positive correlation with the log-transformed peak troponin I (TnI) with statistical significance (r2=0.119, p=0.017; r2=0.225, p=0.006, respectively).
There was a positive correlation between the LnIMRtrue and the FFR0.8. Both of the values were associated with peak TnI. Those values may be used as appropriate surrogate measures of microvascular function after AMI.
Myocardial infarction; Fractional flow reserve, myocardial; Microcirculation; Percutaneous coronary intervention
Duodenal varix bleeding is an uncommon cause of gastrointestinal bleeding in patients with portal hypertension but can cause severe and potentially fatal bleeding. However, the incidence is low and a good treatment method has not been well established yet. Duodenal variceal bleeding can be treated surgically or nonsurgically. We have successfully treated a patient with duodenal variceal bleeding secondary to liver cirrhosis using hemoclips to control the bleeding.
Gastrointestinal bleeding; Duodenal varix; Endoscopic clipping
The present study aimed to identify key metabolites related to weight reduction in humans by studying the metabolic profiles of sera obtained from 34 participants who underwent dietary intervention with black soybean peptides (BSP) for 12 weeks. This research is a sequel to our previous work in which the effects of BSP on BMI and blood composition of lipid were investigated. Sera of the study were subjected to ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and the data were analyzed using partial least-squares discriminate analysis (PLS-DA) score plots. Body mass index and percent body fat of the test group were reduced. Levels of betaine, benzoic acid, pyroglutamic acid, pipecolic acid, N-phenylacetamide, uric acid, l-aspartyl-l-phenylalanine, and lysophosphatidyl cholines (lysoPCs) (C18:1, C18:2, C20:1, and C20:4) showed significant increases. Levels of l-proline, valine, l-leucine/isoleucine, hypoxanthine, glutamine, l-methionine, phenylpyruvic acid, several carnitine derivatives, and lysoPCs (C14:0, PC16:0, C15:0, C16:0, C17:1, C18:0, and C22:0) were significantly decreased. In particular, lysoPC 16:0 with a VIP value of 12.02 is esteemed to be the most important metabolite for evaluating the differences between the 2 serum samples. Our result confirmed weight-lowering effects of BSP, accompanied by favorable changes in metabolites in the subjects' blood. Therefore, this research enables us to better understand obesity and increases the predictability of the obesity-related risk by studying metabolites present in the blood.
Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD+), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD+ affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ∼80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD+ due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels.
hypoglycemia; lactate; microglial activation; neuron death; superoxide
Lung cancer in never-smokers ranks as the seventh most common cause of cancer death worldwide, and the incidence of lung cancer in non-smoking Korean women appears to be steadily increasing. To identify the effect of genetic polymorphisms on lung cancer risk in non-smoking Korean women, we conducted a genome-wide association study of Korean female non-smokers with lung cancer. We analyzed 440,794 genotype data of 285 cases and 1,455 controls, and nineteen SNPs were associated with lung cancer development (P < 0.001). For external validation, nineteen SNPs were replicated in another sample set composed of 293 cases and 495 controls, and only rs10187911 on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, P = 0.025). We confirmed this SNP again in another replication set composed of 546 cases and 744 controls (recessive model, OR of GG, 1.32, P = 0.027). OR and P value in combined set were 1.37 and < 0.001 in additive model, 1.51 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model. The effect of this SNP was found to be consistent only in adenocarcinoma patients (1.36 and < 0.001 in additive model, 1.49 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model). Furthermore, after imputation with HapMap data, we found regional significance near rs10187911, and five SNPs showed P value less than that of rs10187911 (rs12478012, rs4377361, rs13005521, rs12475464, and rs7564130). Therefore, we concluded that a region on chromosome 2 is significantly associated with lung cancer risk in Korean non-smoking women.
Lung Neoplasms; Genome-Wide Association Study; Non-Smoking Women
Siguan acupoints have been used to treat gastrointestinal symptoms in acupuncture practices for a long time. This study aimed to investigate the effects of Siguan acupuncture on gastrointestinal motility under accelerated conditions using a randomized, sham-acupuncture-controlled, crossover study. Twenty-one healthy male subjects were hospitalized and randomized into either a real acupuncture group (at Siguan acupoints) or a sham acupuncture group. Subjects were administered with mosapride citrate (15 mg a day) for 2 days starting 24 hours before the first acupuncture treatment. Immediately after the administration of radio markers, acupuncture treatment was conducted 4 times at 12-hour intervals. Gastrointestinal motility was assessed using radiograph distribution of the radio-markers located in the small intestine, ascending colon, transverse colon, descending colon, rectum, and outside the body immediately after the first acupuncture treatment and at 6, 12, 24, and 48 hours. After a 2-week washout period, the real acupuncture group in the first session was treated with sham acupuncture in the second session, and vice versa. Gastrointestinal motility was generally reduced in the real acupuncture group compared with the sham acupuncture group throughout the 4 different time points. A significant difference was observed at 24 hours following the first acupuncture treatment (P < 0.05).
Here we present an overview of our existing knowledge on the function of RIN4 as a regulator of plant defense and as a guardee of multiple plant R-proteins. Domain analysis of RIN4 reveals two NOI domains. The NOI domain was originally identified in a screen for nitrate induced genes. The domain is comprised of approximately 30 amino acids and contains 2 conserved motifs (PXFGXW and Y/FTXXF). The NOI gene family contains members exclusively from the plant lineage as far back as moss. In addition to the conserved NOI domain, members within the family also contain conserved C-terminal cysteine residue(s) which are sites for acylation and membrane tethering. Other than these two characteristic features, the sequence of the family of NOI-containing proteins is diverse and, with the exception of RIN4, their functions are not known. Recently published interactome data showing interactions between RIN4 and components of the exocyst complex prompt us to raise the hypothesis that RIN4 might be involved in defense associated vesicle trafficking.
Garlic protects against degenerative diseases such as hyperlipidemia and cardiovascular diseases. However, raw garlic has a strong pungency, which is unpleasant. In this study, we examined the effect of high temperature/high pressure-processed garlic on plasma lipid profiles in rats. Sprague–Dawley rats were fed a normal control diet, a high cholesterol (0.5% cholesterol) diet (HCD) only, or a high cholesterol diet supplemented with 0.5% high temperature/high pressure-processed garlic (HCP) or raw garlic (HCR) for 10 weeks. The body weights of the rats fed the garlic-supplemented diets decreased, mostly because of reduced fat pad weights. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride (TG) in the HCP and HCR groups decreased significantly compared with those in the HCD group. Additionally, fecal TC and TG increased significantly in the HCP and HCR groups. It is notable that no significant differences in plasma or fecal lipid profiles were observed between the HCP and HCR groups. High temperature/high pressure-processed garlic contained a higher amount of S-allyl cysteine than raw garlic (P<.05). The results suggest that high temperature/high pressure-processed garlic may be useful as a functional food to improve lipid profiles.
S-allyl cysteine; high temperature/high pressure-processed garlic; plasma lipid profiles
Duodenal duplication cyst is a rare anomaly, totaling only 4% to 12% of gastrointestinal duplications, and is usually encountered during infancy or in early childhood. Most are commonly located posterior to the first or second portion of the duodenum. Presenting signs and symptoms include vomiting, decreased oral intake, periumbilical tenderness, abdominal distention, obstructive jaundice, acute pancreatitis, and gastrointestinal bleeding. The traditional treatment of a duodenal duplication cyst has been complete surgical resection, but very few cases of endoscopic treatment have been reported in the literature. Here, we report a case of duodenal duplication cyst that was manifested by a duodenal polyp.
Duodenum; Duplication cyst; Endoscopic resection
Several studies have shown that epileptic seizures increase hippocampal neurogenesis in the adult. However, the mechanism underlying increased neurogenesis after seizures remains largely unknown. Neurogenesis occurs in the subgranular zone (SGZ) of the hippocampus in the adult brain, although an understanding of why it actively occurs in this region has remained elusive. A high level of vesicular zinc is localized in the presynaptic terminals of the SGZ. Previously, we demonstrated that a possible correlation may exist between synaptic zinc localization and high rates of neurogenesis in this area after hypoglycemia. Using a lithium-pilocarpine model, we tested our hypothesis that zinc plays a key role in modulating hippocampal neurogenesis after seizure. Then, we injected the zinc chelator, clioquinol (CQ, 30 mg/kg), into the intraperitoneal space to reduce brain zinc availability. Neuronal death was detected with Fluoro Jade-B and NeuN staining to determine whether CQ has neuroprotective effects after seizure. The total number of degenerating and live neurons was similar in vehicle and in CQ treated rats at 1 week after seizure. Neurogenesis was evaluated using BrdU, Ki67 and doublecortin (DCX) immunostaining 1 week after seizure. The number of BrdU, Ki67 and DCX positive cell was increased after seizure. However, the number of BrdU, Ki67 and DCX positive cells was significantly decreased by CQ treatment. Intracellular zinc chelator, N,N,N0,N-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), also reduced seizure-induced neurogenesis in the hippocampus. The present study shows that zinc chelation does not prevent neurodegeneration but does reduce seizure-induced progenitor cell proliferation and neurogenesis. Therefore, this study suggests that zinc has an essential role for modulating hippocampal neurogenesis after seizure.
Adaptation of tumor cells to the host is a major cause of cancer progression, failure of therapy, and ultimately death. Immune selection drives this adaptation in human cancer by enriching tumor cells with a cancer stem cell–like (CSC-like) phenotype that makes them resistant to CTL-mediated apoptosis; however, the mechanisms that mediate CSC maintenance and proliferation are largely unknown. Here, we report that CTL-mediated immune selection drives the evolution of tumor cells toward a CSC-like phenotype and that the CSC-like phenotype arises through the Akt signaling pathway via transcriptional induction of Tcl1a by Nanog. Furthermore, we found that hyperactivation of the Nanog/Tcl1a/Akt signaling axis was conserved across multiple types of human cancer. Inhibition of Nanog in a murine model of colon cancer rendered tumor cells susceptible to immune-mediated clearance and led to successful, long-term control of the disease. Our findings establish a firm link among immune selection, disease progression, and the development of a stem-like tumor phenotype in human cancer and implicate the Nanog/Tcl1a/Akt pathway as a central molecular target in this process.
Background: Previous studies have suggested that diabetes mellitus (DM) is an outcome of exposure to air pollution, and metabolic detoxification genes affect air pollution–related outcomes.
Objectives: We evaluated associations between air pollutants and markers of insulin resistance (IR), an underlying mechanism of type 2 DM, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes among elderly participants in the Korean Elderly Environmental Panel (KEEP) study.
Methods: We recruited 560 people ≥ 60 years of age and obtained blood samples from them up to three times between 2008 and 2010. For air pollution exposure, we used ambient air pollutant [i.e., particulate matter ≤ 10 µm in diameter (PM10), sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2)] monitoring data. We measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR. Mixed-effect models were used to estimate associations between air pollutants and IR indices on the same day or lagged up to 10 days prior, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes.
Results: Interquartile range increases in PM10, O3, and NO2 were significantly associated with IR indices, depending on the lag period. Associations were stronger among participants with a history of DM and among those with GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes.
Conclusions: Our results suggest that PM10, O3, and NO2 may increase IR in the elderly, and that GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes may increase susceptibility to potential effects of ambient air pollutants on IR.
air pollution; elderly; genetic polymorphism; insulin resistance
Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients.
Hypoglycemia; Minocycline; Neuronal death; Microglia
The purpose of this study is to evaluate survival and prognostic factors for rectal cancer, including interval between surgery and radiation therapy after surgery, radiation therapy, and chemotherapy.
Materials and Methods
We conducted a retrospective study of 153 patients with rectal cancer who were treated with surgery, radiotherapy with/without chemotherapy at Keimyung University Dongsan Medical Center from January, 1988 to December, 2005. The study included 89 males and 64 females, with a median age of 56 years (range, 23 to 81 years). Tumor, node and metastasis (TNM) was I in 23 patients, II in 39, and III in 91. Radiation therapy was performed on pelvic fields using a median dose of 54 Gy five days per week, 1.8 Gy once per day. Ninety two patients were treated with radiotherapy, 43 with concurrent chemo-radiation therapy and 18 with sequential therapy after surgery. The median follow-up period was 52 months (range, 4 to 272 months). The interval between surgery and radiation was 1-25 weeks (median, 5 weeks).
Two-year and five-year overall survival rate was 64.7% and 46.4%, respectively. Two-year and five-year disease-free-survival (DFS) rate was 58.6% and 43.1%, respectively. Median DFS was 39 months. Loco-regional failure was evident in 10.5% of patients, 8.4% had distant metastasis, and 9.2% had both. In multivariate analysis, TNM stage and interval between surgery and radiation therapy (≤5 weeks vs. >5 weeks; 95% confidence interval, 1.276 to 2.877; hazard ratio, 1.916; p=0.002) were significant prognostic factors of DFS.
Survival rates for rectal cancer after surgery, chemotherapy, and radiation therapy were similar to those reported in previous studies. Starting radiation therapy as soon as possible after surgery, especially within the first five weeks after surgery, is suggested.
Rectal neoplasms; Adjuvant radiotherapy; Drug therapy; Prognosis
Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes. Although mild or moderate hypoglycemia is not life-threatening, if recurrent, it may cause cognitive impairment. In the present study, we sought to determine whether R/M hypoglycemia leads to neuronal death, dendritic injury, or cognitive impairment.
The experiments were conducted in normal and in diabetic rats. Rats were subjected to moderate hypoglycemia by insulin without anesthesia. Oxidative stress was evaluated by 4-Hydroxy-2-nonenal immunostaining and neuronal death was determined by Fluoro-Jade B staining 7 days after R/M hypoglycemia. To test whether oxidative injury caused by NADPH oxidase activation, an NADPH oxidase inhibitor, apocynin, was used. Cognitive function was assessed by Barnes maze and open field tests at 6 weeks after R/M hypoglycemia.
The present study found that oxidative injury was detected in the dendritic area of the hippocampus after R/M hypoglycemia. Sparse neuronal death was found in the cortex, but no neuronal death was detected in the hippocampus. Significant cognitive impairment and thinning of the CA1 dendritic region was detected 6 weeks after hypoglycemia. Oxidative injury, cognitive impairment, and hippocampal thinning after R/M hypoglycemia were more severe in diabetic rats than in non-diabetic rats. Oxidative damage in the hippocampal CA1 dendritic area and microglial activation were reduced by the NADPH oxidase inhibitor, apocynin.
The present study suggests that oxidative injury of the hippocampal CA1 dendritic region by R/M hypoglycemia is associated with chronic cognitive impairment in diabetic patients. The present study further suggests that NADPH oxidase inhibition may prevent R/M hypoglycemia-induced hippocampal dendritic injury.
Recurrent/moderate hypoglycemia; Dendrite; Superoxide; Lipid peroxidation; Neuron death; Microglial activation; NADPH oxidase; Apocynin