Sex differences in in-hospital management in patients with sepsis and septic shock: a prospective multicenter observational study.

Sex differences in the in-hospital management of sepsis exist. Previous studies either included patients with sepsis that was defined using previous definitions of sepsis or evaluated the 3-h bundle therapy. Therefore, this study sought to assess sex differences in 1-h bundle therapy and in-hospital management among patients with sepsis and septic shock, defined according to the Sepsis-3 definitions. This observational study used data from Korean Shock Society (KoSS) registry, a prospective multicenter sepsis registry. Adult patients with sepsis between June 2018 and December 2021 were included in this study. The primary outcome was adherence to 1-h bundle therapy. Propensity score matching (PSM) and multivariable logistic regression analyses were performed. Among 3264 patients with sepsis, 3129 were analyzed. PSM yielded 2380 matched patients (1190 men and 1190 women). After PSM, 1-h bundle therapy was performed less frequently in women than in men (13.0% vs. 19.2%; p < 0.001). Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently in women than in men (25.4% vs. 31.6%, p < 0.001), whereas adequate fluid resuscitation was performed more frequently in women than in men (96.8% vs. 95.0%, p = 0.029). In multivariable logistic regression analysis, 1-h bundle therapy was performed less frequently in women than in men [adjusted odds ratio (aOR) 1.559; 95% confidence interval (CI) 1.245-1.951; p < 0.001] after adjustment. Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently to women than men (aOR 1.339, 95% CI 1.118-1.605; p = 0.002), whereas adequate fluid resuscitation was performed more frequently for women than for men (aOR 0.629, 95% CI 0.413-0.959; p = 0.031). Invasive arterial blood pressure monitoring was performed less frequently in women than in men. Resuscitation fluid, vasopressor, steroid, central-line insertion, ICU admission, length of stay in the emergency department, mechanical ventilator use, and renal replacement therapy use were comparable for both the sexes. Among patients with sepsis and septic shock, 1-h bundle therapy was performed less frequently in women than in men. Continuous efforts are required to increase adherence to the 1-h bundle therapy and to decrease sex differences in the in-hospital management of patients with sepsis and septic shock.

The usefulness of lactate/albumin ratio, C-reactive protein/albumin ratio, procalcitonin/albumin ratio, SOFA, and qSOFA in predicting the prognosis of patients with sepsis who presented to EDs.

PURPOSE: Early identification of sepsis with a poor prognosis in the emergency department (ED) is crucial for prompt management and improved outcomes. This study aimed to examine the predictive value of sequential organ failure assessment (SOFA), quick SOFA (qSOFA), lactate to albumin ratio (LAR), C-reactive protein to albumin ratio (CAR), and procalcitonin to albumin ratio (PAR), obtained in the ED, as predictors for 28-day mortality in patients with sepsis and septic shock. MATERIALS AND METHODS: We included 3499 patients (aged ≥19 years) from multicenter registry of the Korean Shock Society between October 2015 and December 2019. The SOFA score, qSOFA score, and lactate level at the time of registry enrollment were used. Albumin, C-reactive protein, and procalcitonin levels were obtained from the initial laboratory results measured upon ED arrival. We evaluated the predictive accuracy for 28-day mortality using the area under the receiver operating characteristic (AUROC) curve. A multivariable logistic regression analysis of the independent predictors of 28-day mortality was performed. The SOFA score, LAR, CAR, and PAR were converted to categorical variables using Youden's index and analyzed. Adjusting for confounding factors such as age, sex, comorbidities, and infection focus, adjusted odds ratios (aOR) were calculated. RESULTS: Of the 3499 patients, 2707 (77.4%) were survivors, whereas 792 (22.6%) were non-survivors. The median age of the patients was 70 (25th-75th percentiles, 61-78), and 2042 (58.4%) were male. LAR for predicting 28-day mortality had the highest AUROC, followed by the SOFA score (0.715; 95% confidence interval (CI): 0.69-0.74 and 0.669; 95% CI: 0.65-0.69, respectively). The multivariable logistic regression analysis revealed that the aOR of LAR >1.52 was 3.75 (95% CI: 3.16-4.45), and the aOR, of SOFA score at enrollment >7.5 was 2.67 (95% CI: 2.25-3.17). CONCLUSION: The results of this study showed that LAR is a relatively strong predictor of sepsis prognosis in the ED setting, indicating its potential as a straightforward and practical prognostic factor. This finding may assist healthcare providers in the ED by providing them with tools to risk-stratify patients and predict their mortality.

The comparison of psychological scales as hospitalization predictors between adult and elderly suicide attempters.

BACKGROUND: During the process of managing suicide attempters in the emergency department (ED), the importance of hospitalization has been emphasized. Lethality and intent have been suggested as hospitalization determinants of suicide attempters, but their predictive values remain limited in adult and elderly populations. METHODS: Using prospectively collected the ED-based Suicide Registry, data from suicide attempters over 18 years old was retrospectively studied (2010-2020). The enrolled participants were divided into adult (N = 832) and elderly (>65 years, N = 378) groups. Suicide lethality and intent were assessed by the Risk-Rescue Rating Scale (RRRS) and Suicide Intent Scale (SIS), respectively. The moderating effects of age on the relationship between the psychological scales and hospitalization were examined by entering the interaction terms into a multivariable regression model. The predictive ability of each scale for hospitalization was evaluated in terms of performance and goodness-of-fit. RESULTS: Both scales' scores in both age groups were significantly higher in hospitalized patients than non-hospitalized patients. Interaction result indicated that only the odds of RRRS for hospitalization significantly differed by age group. Moreover, the predictive performance for hospitalization significantly differed by age group in RRRS but not SIS. In predicting hospitalization, the AUC of the RRRS was significantly higher than that of the SIS in the elderly group but not in the adult group. Comparing the two groups, the RRRS of the elderly group tended to have higher AUC than the adult group, whereas the AUC of the SIS was similar. The RRRS in both groups had a better overall fit compared to the SIS for hospitalization, but its best overall fit and strength with greater power were observed in the elderly group. CONCLUSIONS: The age-by-RRRS interaction is significantly associated with hospitalization, and the RRRS implementation as a hospitalization determinant is more useful and suitable for elderly suicide attempters than for adult suicide attempters in an emergency setting.

Impact of 1-Hour Bundle Achievement in Septic Shock.

This study aimed to address the impact of 1-hr bundle achievement on outcomes in septic shock patients. Secondary analysis of multicenter prospectively collected data on septic shock patients who had undergone protocolized resuscitation bundle therapy at emergency departments was conducted. In-hospital mortality according to 1-h bundle achievement was compared using multivariable logistic regression analysis. Patients were also divided into 3 groups according to the time of bundle achievement and outcomes were compared to examine the difference in outcome for each group over time: group 1 (≤1 h reference), group 2 (1-3 h) and group 3 (3-6 h). In total, 1612 patients with septic shock were included. The 1-h bundle was achieved in 461 (28.6%) patients. The group that achieved the 1-h bundle did not show a significant difference in in-hospital mortality compared to the group that did not achieve the 1-h bundle on multivariable logistic regression analysis (<1 vs. >1 h) (odds ratio = 0.74, p = 0.091). However, 3- and 6- h bundle achievements showed significantly lower odds ratios of in-hospital mortality compared to the group that did not achieve the bundle (<3 vs. >3 h, <6 vs. >6 h, odds ratio = 0.604 and 0.458, respectively). There was no significant difference in in-hospital mortality over time for group 2 and 3 compared to that of group 1. One-hour bundle achievement was not associated with improved outcomes in septic shock patients. These data suggest that further investigation into the clinical implications of 1-h bundle achievement in patients with septic shock is warranted.

Acute Phlegmonous Gastritis Complicated by Subphrenic Abscess.

BACKGROUND: Phlegmonous gastritis (PG) is a rare and potentially fatal disease characterized by bacterial infection of the gastric wall. However, its clinical features are nonspecific, which may delay its diagnosis and treatment. CASE REPORT: We report a case of a previously healthy 53-year-old woman with localized PG complicated by subphrenic abscess formation who was treated successfully with antibiotics and percutaneous catheter drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early diagnosis and treatment initiation are important to improving outcomes. Emergency physicians should consider PG a differential diagnosis of acute abdomen.

Time to Antibiotics and the Outcome of Patients with Septic Shock: A Propensity Score Analysis.

BACKGROUND: Current sepsis guidelines recommend administration of antibiotics within 1 hour of emergency department (ED) triage. However, the quality of the supporting evidence is moderate, and studies have shown mixed results regarding the association between antibiotic administration timing and outcomes in septic shock. We investigated to evaluate the association between antibiotic administration timing and in-hospital mortality in septic shock patients in the ED, using propensity score analysis. METHODS: An observational study using a prospective, multicenter registry of septic shock, comprising data collected from 10 EDs, was conducted. Septic shock patients were included, and patients were divided into 4 groups by the interval from triage to first antibiotic administration: group 1 (≤1 hour; reference), 2 (1-2 hours), 3 (2-3 hours), and 4 (>3 hours). The primary endpoint was in-hospital mortality. After inverse probability of treatment weighting, the outcomes of the groups were compared. RESULTS: A total of 2250 septic shock patients were included, and the median time to first antibiotic administration was 2.29 hours. The in-hospital mortality of groups 2 and 4 were significantly higher than those of group 1 (odds ratio [OR] 1.248; 95% confidence interval [CI], 1.053-1.478; P = .011; OR 1.419; 95% CI, 1.203-1.675; P < .001, respectively), but those of group 3 was not (OR 1.186; 95% CI, 0.999-1.408; P = .052). Subgroup analyses of patients (n = 2043) with appropriate antibiotics presented similar results. CONCLUSIONS: In patients with septic shock, rapid administration of antibiotics was generally associated with a decrease in in-hospital mortality, but no "every hour delay" was seen.

Impact of timing to source control in patients with septic shock: A prospective multi-center observational study.

PURPOSE: Current guidelines recommend that rapid source control should be adopted in patients not >6-12 h after sepsis is diagnosed. However, evidence level of this guideline is not specified, and there is no previous study on patients with septic shock visiting the emergency department (ED). Therefore, we aimed to assess the impact of rapid source control in patients with septic shock visiting the ED. MATERIALS AND METHODS: In a prospective, observational, multicenter, registry-based study in 11 EDs, Cox proportional hazards model was used to assess the independent effect of source control and time to source control on 28-day mortality. RESULTS: Cox proportional hazard models revealed that 28-day mortality was significantly lower in patients who underwent source control (HR 0.538 (0.389-0.744), p < .001). However, no significant association between the performance of source control after 6 h or 12 h from enrollment and 28-day mortality was noted. CONCLUSIONS: Patients with septic shock visiting the ED who underwent source control showed better outcomes than those who did not. We failed to demonstrate the performance of rapid source control reduced the 28-day mortality in septic shock patients. Further studies are required to determine the impact of rapid source control in sepsis and septic shock.

Femoral Intertrochanteric Fractures of the Patients in the Emergency Department due to Minor Falls: Special Consideration in the Middle-old to Oldest-old Patients.

BACKGROUND: The older population (≥65 years) has rapidly increased in size in recent years. Among them, the middle-to-oldest-old (≥75 years) tend to have a poor health status. Therefore, subdivision and evaluation of older patients with traumatic injury are required. We focused on the risk of femoral intertrochanteric fractures occurring in older adults due to minor falls and compared young-old and middle-to-oldest-old populations. METHODS: The medical records of patients who visited the emergency center due to hip injuries between March 2017 and March 2019 were retrospectively analyzed. Patients were divided into older adult (≥65 years) and non-older (age 18-64 years) groups; the older adult group was subdivided into young-old (65-74 years), middle-old (75-84 years), and oldest-old (≥85 years) groups. This study investigated the occurrence rate of femoral intertrochanteric fractures and related factors. RESULTS: The older adult group had a higher incidence of femoral intertrochanteric fractures than that in the non-older adult group (95.3% vs. 4.7%, p<0.001). However, there was no significant difference between young-old and non-older groups (58.8% vs. 41.2%, p=0.145). Middle-old to oldest-old age and osteoporosis were associated with an increased incidence of femoral intertrochanteric fractures (p<0.001, p=0.004). CONCLUSION: A higher incidence of femoral intertrochanteric fractures from minor falls was found among middle-old to oldest-old patients compared to that in young-old patients. Therefore, physicians should perform more thorough physical examinations and radiograph reading in middle-old to oldest-old patients even if the patients do not complain of pain.

Clinical outcome comparison of patients with septic shock defined by the new sepsis-3 criteria and by previous criteria.

BACKGROUND: We compared the clinical characteristics and outcomes between the new definition of sepsis-3 septic shock and the definition previously used from 1991 until recently. METHODS: We conducted an observational study using a prospective, multi-center registry of septic shock from October 2015 to February 2017. Registry data were collected by 10 emergency departments (EDs) in tertiary hospitals that are members of the Korean Shock Society. Data on septic shock patients who met the previous septic shock definition were collected. The patients were divided into a sepsis-3 defined septic shock group, made up of those who met the new criteria for refractory hypotension with hyperlactatemia, and a group of those who met only the 1991 definition for septic shock. The primary outcome was 90-day mortality, and secondary outcomes were 28-day mortality and in-hospital mortality. RESULTS: Of all 1,028 included patients, 574 (55.8%) met the septic shock criteria for sepsis-3, leaving 454 patients who met only the previous definition. Those who met the sepsis-3 criteria demonstrated higher comorbidity than those who met the previous definition (83.1% vs. 75.3%, P<0.01), but there was no difference in infection focus. The sequential organ failure assessment (SOFA) (initial/maximal), the acute physiology, and the chronic health evaluation II scores were significantly higher in for those who met the sepsis-3 criteria [6.5±3.1 vs. 5.0±2.9, 9.3±3.8 vs. 6.6±3.4, and 20.0 (15.0-26.0) vs. 15.0 (10.0-20.3), respectively; P<0.01]. The 90-day mortality was significantly higher in the sepsis-3 group (32.1% vs. 23.3%; P<0.01). In-hospital and 28-day mortality were also higher in the sepsis-3 group (26.8% vs. 17.1% and 25.1% vs. 16.5%, respectively; P<0.01). CONCLUSIONS: The new definition of septic shock successfully selected patients with greater severities and worse outcomes.

Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study.

BACKGROUND: Septic shock can be defined both by the presence of hyperlactatemia and need of vasopressors. Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition). However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation. METHODS: This observational study was performed using a prospective, multi-center registry of septic shock, with the participation of 10 hospitals in the Korean Shock Society, between October 2015 and February 2017. We compared the 28-day mortality between patients who were excluded from the new definition (defined as lactate level <2 mmol/L after volume resuscitation) and those who were not (≥2 mmol/L after volume resuscitation), from among a cohort of patients with refractory hypotension, and requiring the use of vasopressors. Other outcome variables such as in-hospital mortality, intensive care unit (ICU) stay (days), Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. RESULTS: Of 567 patients with refractory hypotension, requiring the use of vasopressors, 435 had elevated lactate levels, while 83 did not have elevated lactate levels (either initially or after volume resuscitation), and 49 (8.2%) had elevated lactate levels initially, which normalized after fluid resuscitation. Thus, these 49 patients were excluded by the new definition of septic shock. These patients, in whom perfusion was restored, demonstrated significantly lower age, platelet count, and initial and subsequent lactate levels (all p < 0.01). Similarly, significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, p = 0.02). In-hospital mortality and the maximum SOFA score were also significantly lower in the excluded patients group (p = 0.03, both). CONCLUSIONS: It seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation. However, owing to the small number of patients in whom lactate levels were improved, further study is warranted.

Prognostic Value of The Lactate/Albumin Ratio for Predicting 28-Day Mortality in Critically ILL Sepsis Patients.

AIM: The aim of this study was to evaluate the clinical utility of the lactate/albumin (L/A) ratio as a predictive factor of 28-day mortality in critically ill sepsis patients. METHODS: This is a retrospective observational study from a prospectively collected multicenter registry of 10 emergency departments (EDs) in teaching hospitals that participated in the Korean Shock Society. It enrolled patients who were 19 years of age or older who had a suspected or confirmed infection and evidence of refractory hypotension or hypoperfusion. The prognostic performance of the L/A ratio and lactate level for predicting 28-day mortality was assessed. Lactate and albumin levels were measured immediately after ED arrival. RESULTS: A total of 946 patients were included, with 22.5% overall 28-day mortality. The area under the receiver operating characteristic curve (AUROC) value of the L/A ratio (0.69, 95% confidence interval [CI] 0.64-0.73, P < 0.01) was higher than that of lactate (0.65, 95% CI 0.61-0.70, P < 0.01) for predicting 28-day mortality. The optimal cutoff of the L/A ratio was 1.32. The AUROC value of the L/A ratio was better than that of lactate regardless of lactate level (normal [<2.0 mmol/L]: 0.68 vs. 0.55; intermediate [≥2.0, < 4.0 mmol/L]: 0.65 vs. 0.50; high [≥4.0 mmol/L]: 0.66 vs. 0.62). In the subgroup with decreased lactate elimination, the AUROC value of the L/A ratio was also significantly higher than that of lactate (hepatic dysfunction: 0.70 vs. 0.66; renal dysfunction: 0.71 vs. 0.67). The L/A ratio cut-off and hypoalbminemia showed further discriminative value for 28-day mortality even in patients with normal or intermediate lactate levels. CONCLUSIONS: The prognostic performance of the L/A ratio was superior to that of a single lactate measurement for predicting 28-day mortality of critically ill sepsis patients. L/A ratio can be a useful prognostic factor regardless of initial lactate level and the presence of hepatic or renal dysfunction.

Korean Shock Society septic shock registry: a preliminary report.

OBJECTIVE: To evaluate the clinical characteristics, therapeutic interventions, and outcomes of patients with septic shock admitted to the emergency department (ED). METHODS: This study was a preliminary, descriptive analysis of a prospective, multi-center, observational registry of the EDs of 10 hospitals participating in the Korean Shock Society. Patients aged 19 years or older who had a suspected or confirmed infection and evidence of refractory hypotension or hypoperfusion were included. RESULTS: A total of 468 patients were enrolled (median age, 71.3 years; male, 55.1%; refractory hypotension, 82.9%; hyperlactatemia without hypotension, 17.1%). Respiratory infection was the most common source of infection (31.0%). The median Sepsis-related Organ Failure Assessment score was 7.5. The sepsis bundle compliance was 91.2% for lactate measurement, 70.3% for blood culture, 68.4% for antibiotic administration, 80.3% for fluid resuscitation, 97.8% for vasopressor application, 68.0% for central venous pressure measurement, 22.0% for central venous oxygen saturation measurement, and 59.2% for repeated lactate measurement. Among patients who underwent interventions for source control (n=117, 25.1%), 43 (36.8%) received interventions within 12 hours of ED arrival. The in-hospital, 28-day, and 90-day mortality rates were 22.9%, 21.8%, and 27.1%, respectively. The median ED and hospital lengths of stay were 6.8 hours and 12 days, respectively. CONCLUSION: This preliminary report revealed a mortality of over 20% in patients with septic shock, which suggests that there are areas for improvement in terms of the quality of initial resuscitation and outcomes of septic shock patients in the ED.

Near-complete optic nerve transection by high-pressure air.

The use of high-pressure air instruments has become more common. Consequently, there have been a number of cases of orbital emphysema caused by contact with high-pressure air. In this case, a 62-year-old male patient visited an emergency medical center after his left eye was shot by an air compressor gun that was used to wash cars. Lacerations were observed in the upper and lower eyelids of his left eye. Radiological examinations revealed orbital emphysema, optic nerve transection, pneumocephalus, and subcutaneous emphysema in the face, neck, shoulder, and mediastinum. Canalicular injury repair was performed, and the emphysema resolved. However, there was near-complete vision loss in the patient's left eye. Because most optic nerve transections occur after a severe disruption in bone structure, pure optic nerve transections without any injury of the bone structure, as in the present case, is extremely rare.

A Randomized Controlled Trial of Compression Rates during Cardiopulmonary Resuscitation.

UNLABELLED: The objective of this study was to compare the efficacy of cardiopulmonary resuscitation (CPR) with 120 compressions per minute (CPM) to CPR with 100 CPM in patients with non-traumatic out-of-hospital cardiac arrest. We randomly assigned patients with non-traumatic out-of-hospital cardiac arrest into two groups upon arrival to the emergency department (ED). The patients received manual CPR either with 100 CPM (CPR-100 group) or 120 CPM (CPR-120 group). The primary outcome measure was sustained restoration of spontaneous circulation (ROSC). The secondary outcome measures were survival discharge from the hospital, one-month survival, and one-month survival with good functional status. Of 470 patients with cardiac arrest, 136 patients in the CPR-100 group and 156 patients in the CPR-120 group were included in the final analysis. A total of 69 patients (50.7%) in the CPR-100 group and 67 patients (42.9%) in the CPR-120 group had ROSC (absolute difference, 7.8% points; 95% confidence interval [CI], -3.7 to 19.2%; P = 0.183). The rates of survival discharge from the hospital, one-month survival, and one-month survival with good functional status were not different between the two groups (16.9% vs. 12.8%, P = 0.325; 12.5% vs. 6.4%, P = 0.073; 5.9% vs. 2.6%, P = 0.154, respectively). We did not find differences in the resuscitation outcomes between those who received CPR with 100 CPM and those with 120 CPM. However, a large trial is warranted, with adequate power to confirm a statistically non-significant trend toward superiority of CPR with 100 CPM. ( CLINICAL TRIAL REGISTRATION INFORMATION: www.cris.nih.go.kr, cris.nih.go.kr number, KCT0000231).

Chemical analysis of Punica granatum fruit peel and its in vitro and in vivo biological properties.

BACKGROUND: The medical application of pomegranate fruits and its peel is attracted human beings. The aim of the present study was to evaluate the in vitro α-Glucosidase inhibition, antimicrobial, antioxidant property and in vivo anti-hyperglycemic activity of Punica granatum (pomegranate) fruit peel extract using Caenorhabditis elegans. METHODS: Various invitro antioxidant activity of fruit peel extracts was determined by standard protocol. Antibacterial and antifungal activities were determined using disc diffusion and microdilution method respectively. Anti-hyperglycemic activity of fruit peel was observed using fluorescence microscope for in vivo study. RESULTS: The ethyl acetate extract of P. granatum fruit peel (PGPEa) showed α-Glucosidase inhibition upto 50 % at the concentration of IC50 285.21 ± 1.9 µg/ml compared to hexane and methanol extracts. The total phenolic content was highest (218.152 ± 1.73 mg of catechol equivalents/g) in ethyl acetate extract. PGPEa showed more scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) with IC50 value 302.43 ± 1.9 µg/ml and total antioxidant activity with IC50 294.35 ± 1.68 µg/ml. PGPEa also showed a significant effecton lipid peroxidation IC50 208.62 ± 1.68 µg/ml, as well as high reducing power. Among the solvents extracts tested, ethyl acetate extract of fruit peel showed broad spectrum of antimicrobial activity. Ethyl acetate extract supplemented C.elegans worms showed inhibition of lipid accumulation similar to acarbose indicating good hypoglycemic activity. The normal worms compared to test (ethyl acetate extract supplemented) showed the highest hypoglycaemic activity by increasing the lifespan of the worms. GC-MS analysis of PGPEa showed maximum amount of 5-hydroxymethylfurfural and 4-fluorobenzyl alcohol (48.59 %). CONCLUSION: In the present investigation we observed various biological properties of pomegranate fruit peel. The results clearly indicated that pomegranate peel extract could be used in preventing the incidence of long term complication of diabetics.

Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups.

PURPOSE: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurologic morbidity in infants and children. We investigated the effects of pentoxifylline, a methylxanthine derivative and type-4 phosphodiesterase inhibitor, on short-term memory and apoptotic neuronal cell death in the hippocampus following perinatal hypoxic-ischemia in newborn rats. METHODS: We used a step-down avoidance task to evaluate short-term memory and 3ʹ-5ʹ-cyclic adenosine monophosphate (cAMP) assay to detect cAMP levels. We evaluated apoptosis using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for evidence of DNA fragmentation, immunohistochemistry for caspase-3 levels, and western blot for Bcl-2 and Bax. RESULTS: Perinatal hypoxic-ischemic injury increased apoptotic cell death in the hippocampus, resulting in impaired short-term memory with decreased cAMP levels. Pentoxifylline treatment improved short-term memory by suppressing apoptotic cell death in the hippocampus with elevated cAMP levels. CONCLUSIONS: Pentoxifylline ameliorated perinatal hypoxic-ischemia in rat pups. This alleviating effect could be ascribed to the inhibition apoptosis due to increased cAMP production by pentoxifylline.

Antitumor Effect of the Mannich Base(1,3-bis-((3-Hydroxynaphthalen-2-yl)phenylmethyl)urea) on Hepatocellular Carcinoma.

The present study was designed to evaluate the antitumor effects of the synthetic Mannich base 1,3-bis-((3-hydroxynaphthalen-2-yl)phenylmethyl)urea (1,3-BPMU) against HEP-G2 hepatoma cells and diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in albino rats. In vitro analysis results revealed that 1,3-BPMU showed significant cytotoxicity and cell growth inhibition in HEP-G2 hepatoma cells in a concentration-dependent manner. Furthermore, flow cytometry results indicated that 1,3-BPMU enhanced early and late apoptosis. The maximum apoptosis was exhibited at a concentration of 100 µg/mL of 1,3-BPMU. In in vivo analysis, DEN treatment increased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5'NT with decreased antioxidant activity as compared to control rats. However, 1,3-BPMU treatment to DEN-induced rats decreased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5'NT and increased the activities of SOD, CAT, GPx, GST and GR (p < 0.05). Furthermore, 1,3-BPMU enhanced the apoptosis via upregulation of caspase-3 and caspase-9 and the downregulation of Bcl-2 and Bcl-XL mRNA expression as compared to DEN-induced rats. Histological and ultrastructural investigation showed that 1,3-BPMU treatment renovated the internal architecture of the liver in DEN-induced rats. In this study, the molecular and pre-clinical results obtained by treatment of DEN-induced rats with 1,3-BPMU suggested that 1,3-BPMU might be considered as an antitumor compound in the future.

Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury.

PURPOSE: Traumatic brain injury (TBI) causes cognitive impairments, motor deficits, and neuropsychiatric/behavioral deficits problems. Transplantation of bone marrow stromal cells (BMSCs) facilitates functional recovery from brain insults. Treadmill exercise increases neurogenesis and inhibits apoptosis. In this study, we investigated the effects of BMSC transplantation in combination with treadmill exercise on memory function, by evaluating its effect on neurogenesis and apoptosis in the hippocampus following TBI. METHODS: TBI was induced using an electromagnetic-controlled cortical impact device. BMSCs were transplanted into both sides of traumatic scar region 1 week after TBI induction. One week after transplantation of BMSCs, the rats in the exercise groups were trained to run on a treadmill for 30 minutes once daily for 28 days. Step-down avoidance task and radial 8-arm maze test were conducted. Levels of 5-bromo-2ʹ-deoxyuridine and caspase-3 were evaluated using immunohistochemistry. Western blot was used to evaluate the expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), total-extracellular signal-regulated kinase 1 and 2 (t-ERK1/2), phosphorylated-ERK1/2 (p-ERK1/2), Bcl-2, and Bax. RESULTS: TBI deteriorated memory function, suppressed neurogenesis, and accelerated apoptosis in the hippocampus. Treadmill exercise and BMSC transplantation independently improved memory function by increasing neurogenesis with suppression of apoptosis through the BDNF-ERK pathway in the TBI-induced rats. Combination of BMSC transplantation with treadmill exercise showed additional enhancement of neurogenesis and suppression of apoptosis in the hippocampus. CONCLUSIONS: The present study shows that treadmill exercise may aid the therapeutic effect of BMSC transplantation on TBI in rats.

Association Study of Polymorphisms of Epidermal Growth Factor and Epidermal Growth Factor Receptor With Benign Prostatic Hyperplasia in a Korean Population.

PURPOSE: Recent studies have suggested that specific single-nucleotide polymorphisms (SNPs) contribute to the clinical features of benign prostatic hyperplasia (BPH). In this study, we investigated the relationships of genetic polymorphisms of the epidermal growth factor (EGF) gene and the epidermal growth factor receptor (EGFR) gene with BPH. METHODS: A total of 218 patients with BPH were enrolled in this study. We evaluated the relationship between eight SNPs in the EGF and EGFR genes and prostate volume, prostate-specific antigen (PSA), and International Prostate Symptom Score of BPH patients. Each SNP was genotyped by direct sequencing. Statistical analysis applying codominant, dominant, recessive, and log-additive models was performed via logistic regression. RESULTS: The rs11568943 and rs11569017 SNPs in the EGF gene showed significant associations with prostate volume (rs11568943: P=0.038 in the log-additive model, P=0.024 in the allele distribution; rs11569017, P=0.031 in the dominant model, P=0.028 in the log-additive model, P=0.020 in the allele distribution). Additionally, the rs3756261, rs11568943, and rs11569017 SNPs of the EGF gene and the rs2293347 SNP of the EGFR gene were associated with PSA levels (P<0.05 in each model, respectively). CONCLUSIONS: These results suggest that the EGF gene may affect prostate volume. In addition, the EGF and EGFR genes may be associated with PSA levels in patients with BPH.