Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

MRI Detection of Carotid Intraplaque Hemorrhage and Postintervention Cognition.

BACKGROUND AND PURPOSE: Cognitive improvement has been reported after carotid revascularization and attributed to treating stenosis and correcting hypoperfusion. This study investigated the effect of carotid intraplaque hemorrhage on postintervention cognition. MATERIALS AND METHODS: In this institutional review board-approved single-center study, consecutive patients scheduled for carotid surgery were recruited for preoperative carotid MR imaging (MPRAGE) and pre- and postintervention cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status. Pre- and postintervention scores were compared using t tests and multivariable linear regression. RESULTS: Twenty-three participants were included, with endarterectomy performed in 20 (87%) and angioplasty/stent placement, in 3 (13%). Overall, statistically significant improvements occurred in the pre- versus postintervention mean Total Scale score (92.1 [SD, 15.5] versus 96.1 [SD, 15.8], P = .04), immediate memory index (89.4 [SD, 18.2] versus 97.7 [SD, 14.9], P < .001), and verbal index (96.1 [SD, 14.1] versus 103.0 [SD, 12.0], P = .002). Intraplaque hemorrhage (+) participants (n = 11) had no significant improvement in any category, and the attention index significantly decreased (99.4 [SD, 18.0] versus 93.5 [SD, 19.4], P = .045). Intraplaque hemorrhage (-) participants (n = 12) significantly improved in the Total Scale score (86.4 [SD, 11.8] versus 95.5 [SD, 12.4], P = .004), immediate memory index (82.3 [SD, 14.6] versus 96.2 [SD, 14.1], P = .002), delayed memory index (94.3 [SD, 14.9] versus 102.4 [SD, 8.0], P = .03), and verbal index (94.3 [SD, 13.2] versus 101.5 [SD, 107.4], P = .009). Postintervention minus preintervention scores for intraplaque hemorrhage (+) versus (-) groups showed statistically significant differences in the Total Scale score (-0.4 [SD, 6.8] versus 8.0 [SD, 8.5], P = .02), attention index (-5.9 [SD, 8.5] versus 4.3 [SD, 11.9], P = .03), and immediate memory index (4.2 [SD, 6.7] versus 12.2 [SD, 10.2], P = .04). CONCLUSIONS: Cognitive improvement was observed after carotid intervention, and this was attributable to intraplaque hemorrhage (-) plaque. MR imaging detection of intraplaque hemorrhage status may be an important determinant of cognitive change after intervention.

Vessel Wall Enhancement on Black-Blood MRI Predicts Acute and Future Stroke in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a known risk factor for ischemic stroke though angiographic imaging is often negative. Our goal was to determine the relationship between vessel wall enhancement (VWE) in acute and future ischemic stroke in CAA patients. MATERIALS AND METHODS: This was a retrospective study of patients with new-onset neurologic symptoms undergoing 3T vessel wall MR imaging from 2015 to 2019. Vessel wall enhancement was detected on pre- and postcontrast flow-suppressed 3D T1WI. Interrater agreement was evaluated in cerebral amyloid angiopathy-positive and age-matched negative participants using a prevalence- and bias-adjusted kappa analysis. In patients with cerebral amyloid angiopathy, multivariable Poisson and Cox regression were used to determine the association of vessel wall enhancement with acute and future ischemic stroke, respectively, using backward elimination of confounders to P < .20. RESULTS: Fifty patients with cerebral amyloid angiopathy underwent vessel wall MR imaging, including 35/50 (70.0%) with ischemic stroke and 29/50 (58.0%) with vessel wall enhancement. Prevalence- and bias-corrected kappa was 0.82 (95% CI, 0.71-0.93). The final regression model for acute ischemic stroke included vessel wall enhancement (prevalence ratio = 1.5; 95% CI, 1.1-2.2; P = .022), age (prevalence ratio = 1.02; 95% CI, 1.0-1.05; P = .036), time between symptoms and MR imaging (prevalence ratio = 0.9; 95% CI, 0.8-0.9; P < .001), and smoking (prevalence ratio = 0.7; 95% CI, 0.5-1.0; P = .042) with c-statistic = 0.92 (95% CI, 0.84-0.99). Future ischemic stroke incidence with cerebral amyloid angiopathy was 49.7% (95% CI, 34.5%-67.2%) per year over a total time at risk of 37.5 person-years. Vessel wall enhancement-positive patients with cerebral amyloid angiopathy demonstrated significantly shorter stroke-free survival with 63.9% (95% CI, 43.2%-84.0%) versus 32.2% (95% CI, 14.4%-62.3%) ischemic strokes per year, chi-square = 4.9, P = .027. The final model for future ischemic stroke had a c-statistic of 0.70 and included initial ischemic stroke (hazard ratio = 3.4; 95% CI, 1.0-12.0; P = .053) and vessel wall enhancement (hazard ratio = 2.5; 95% CI, 0.9-7.0; P = .080). CONCLUSIONS: Vessel wall enhancement is associated with both acute and future stroke in patients with cerebral amyloid angiopathy.

Risk factors of COVID-19 mortality: a systematic review of current literature and lessons from recent retracted articles.

OBJECTIVE: Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. Therefore, we aimed to analyze the same clinical issues through an improved research method and to find out the differences from the retracted papers. We systematically reviewed pre-existing literature, and compared the results with those of the retracted papers to gain a novel insight. MATERIALS AND METHODS: We extracted common risk factors identified in two retracted papers, and conducted relevant publication search until June 26, 2020 in PubMed. Then, we analyzed the risk factors for COVID-19 mortality and compared them to those of the retracted papers. RESULTS: Our systematic review demonstrated that most demographic and clinical risk factors for COVID-19 mortality were similar to those of the retracted papers. However, while the retracted paper indicated that both (hydroxy)chloroquine monotherapy and combination therapy with macrolide were associated with higher risk of mortality, our study showed that only combination therapy of hydroxychloroquine and macrolide was associated with higher risk of mortality (odds ratio 2.33; 95% confidence interval 1.63-3.34). In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). CONCLUSIONS: When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies, we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients.

Retrospective evaluation of the efficacy of minimally invasive, fluoroscopic-assisted reduction and stabilisation of unicondylar humeral fractures.

OBJECTIVE: This study evaluated the proficiency in executing closed, fluoroscopic-assisted reduction of unicondylar humeral fractures. The following were hypothesised: experienced surgeons would be highly successful in performing closed reduction; body weight, time to surgery and surgeon experience would influence the reduction method; and the reduction method would not affect technical aspects of the repair. METHODS: All unicondylar humeral fractures stabilised between January 2007 and January 2017 were reviewed. Signalment and time to surgery, experience of the attending surgeon, and the initial and definitive reduction methods were recorded. Initial and subsequent postoperative radiographs were used to assess fracture reduction, implant placement and complications. Univariate polychotomous logistic regressions, Fisher's exact test, Kruskal-Wallis rank sums non-parametric test or equivalence tests were used to compare parameters evaluated based on the approach employed (P < 0.05 significant). RESULTS: A total of 36 dogs with 37 fractures were identified (median weight: 5.4 kg; median time to surgery: 3 days). Of these, 11 of 15 attempted closed reductions were successful. Successful closed reductions had shorter times to surgery than limited open or open reductions (P = 0.009). Age, weight and surgeon experience did not influence the definitive reduction method. Technical aspects of reduction and stabilisation were similar among the reduction methods. Surgery times were shorter for closed reductions (P = 0.034). Of the fractures, 75% healed without complications and 85% had excellent long-term function. CONCLUSION: The results suggested that closed, fluoroscopic-assisted reduction is a proficient (73% successful) and efficient (shorter surgery times with comparable technical results compared with other limited open and open reduction) means of stabilising acute unicondylar humeral fractures.

Electroencephalographic markers of brain development during sevoflurane anaesthesia in children up to 3 years old.

BACKGROUND: General anaesthetics generate spatially defined brain oscillations in the EEG that relate fundamentally to neural-circuit architecture. Few studies detailing the neural-circuit activity of general anaesthesia in children have been described. The study aim was to identify age-related changes in EEG characteristics that mirror different stages of early human brain development during sevoflurane anaesthesia. METHODS: Multichannel EEG recordings were performed in 91 children aged 0-3 yr undergoing elective surgery. We mapped spatial power and coherence over the frontal, parietal, temporal, and occipital cortices during maintenance anaesthesia. RESULTS: During sevoflurane exposure: (i) slow-delta (0.1-4 Hz) oscillations were present in all ages, (ii) theta (4-8 Hz) and alpha (8-12 Hz) oscillations emerge by ∼4 months, (iii) alpha oscillations increased in power from 4 to 10 months, (iv) frontal alpha-oscillation predominance emerged at ∼6 months, (v) frontal slow oscillations were coherent from birth until 6 months, and (vi) frontal alpha oscillations became coherent ∼10 months and persisted in older ages. CONCLUSIONS: Key developmental milestones in the maturation of the thalamo-cortical circuitry likely generate changes in EEG patterns in infants undergoing sevoflurane general anaesthesia. Characterisation of anaesthesia-induced EEG oscillations in children demonstrates the importance of developing age-dependent strategies to monitor properly the brain states of children receiving general anaesthesia. These data have the potential to guide future studies investigating neurodevelopmental pathologies involving altered excitatory-inhibitory balance, such as epilepsy or Rett syndrome.

Immunoreduction of ocular surface tumours with intralesional interferon alpha-2a.

PurposeTo share our initial experience in the use of intralesional interferon alpha-2a at primary presentation in ocular surface tumours as a method of immunoreduction prior to definitive surgical management.MethodsCase series of patients referred to Sheffield Ocular Oncology Service with rapidly growing ocular surface tumours, treated with intralesional interferon alpha-2a at first presentation prior to definitive surgical management.ResultsAll three patients, two with conjunctival melanoma and one with ocular surface squamous neoplasia (OSSN) demonstrated immunoreduction of tumour without any adverse side effects.ConclusionsInterferon alpha-2a is effective in conjunctival melanoma and OSSN. Intralesional interferon at first presentation may be used for immunoreduction prior to definitive surgical management. This may improve surgical and long-term outcomes, improve patient experience, and help meet cancer treatment targets.

Association of high-dose postoperative opioids with recurrence risk in esophageal squamous cell carcinoma: reinterpreting ERAS protocols for long-term oncologic surgery outcomes.

Esophageal squamous cell carcinoma (ESCC) is associated with a poor prognosis and high postoperative recurrence rate. Although postoperative opioid use has been associated with cancer recurrence, its relevance in ESCC has not been determined. Therefore, this study investigated whether high-dose postoperative opioid use was associated with recurrence risk in patients with ESCC. For this retrospective analysis, the medical records of patients who were diagnosed with ESCC and who underwent surgery between January 2006 and December 2010 in the National Cancer Center, Korea were evaluated. Total opioid administration over a 10-day period, from during surgery to postoperative day 9, was calculated. A cutoff value was determined using receiver operating characteristic curve analysis, and patients were classified into the high-use and low-use groups. The primary and secondary outcomes of the study were freedom from recurrence and overall survival, respectively. After propensity score matching, the effect of opioid use on freedom from recurrence and overall survival was evaluated using the Kaplan-Meier method. The final analysis set included 258 patients. The cumulative opioid dose cutoff point was 1783.5 mg of oral morphine. High-dose postoperative opioid use was a significant factor affecting recurrence (Hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.583-2.954; P < 0.0001). In contrast, postoperative opioid use was not associated with death (HR, 1.274; 95% CI, 0.922-1.761; P = 0.1422). In patients with ESCC, compared with low-dose opioid use, high-dose intraoperative and postoperative opioid use was significantly associated with an increased risk of recurrence. However, opioid dosage did not affect overall survival.

Development of an E-learning System for the Endoscopic Diagnosis of Early Gastric Cancer: An International Multicenter Randomized Controlled Trial.

BACKGROUND: In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness. METHODS: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results. FINDINGS: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001). INTERPRETATION: This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).

Prediction of Carotid Intraplaque Hemorrhage Using Adventitial Calcification and Plaque Thickness on CTA.

BACKGROUND AND PURPOSE: Carotid intraplaque hemorrhage is associated with stroke, plaque thickness, stenosis, ulceration, and adventitial inflammation. Conflicting data exist on whether calcification is a marker of plaque instability, and no data exist on adventitial calcification. Our goal was to determine whether adventitial calcification and soft plaque (a rim sign) help predict carotid intraplaque hemorrhage. MATERIALS AND METHODS: This was a retrospective cohort study of 96 patients who underwent carotid MRA and CTA within 1 month, from 2009 to 2016. We excluded occlusions (n = 4) and near occlusions (n = 0), leaving 188 carotid arteries. Intraplaque hemorrhage was detected by using MPRAGE. Calcification, adventitial pattern, stenosis, maximum plaque thickness (total, soft, and hard), ulceration, and intraluminal thrombus on CTA were recorded. Atherosclerosis risk factors and medications were recorded. We used mixed-effects multivariable Poisson regression, accounting for 2 vessels per patient. For the final model, backward elimination was used with a threshold of P < .10. Receiver operating characteristic analysis determined intraplaque hemorrhage by using the area under the curve. RESULTS: Our final model included the rim sign (prevalence ratio = 11.9, P < .001) and maximum soft-plaque thickness (prevalence ratio = 1.2, P = .06). This model had excellent intraplaque hemorrhage prediction (area under the curve = 0.94), outperforming the rim sign, maximum soft-plaque thickness, NASCET stenosis, and ulceration (area under the curve = 0.88, 0.86, 0.77, and 0.63, respectively; P < .001). Addition of the rim sign performed better than each marker alone, including maximum soft-plaque thickness (area under the curve = 0.94 versus 0.86, P < .001), NASCET stenosis (area under the curve = 0.90 versus 0.77, P < .001), and ulceration (area under the curve = 0.90 versus 0.63, P < .001). CONCLUSIONS: The CTA rim sign of adventitial calcification with internal soft plaque is highly predictive of carotid intraplaque hemorrhage.

Entosis: Cell-in-Cell Formation that Kills Through Entotic Cell Death.

Entosis is a cell-in-cell formation mechanism that targets viable cells for uptake in epithelial cell cultures and human tumors. Entotic cells control their own engulfment, by invading into their hosts in a Rho-GTPase and actomyosin-dependent manner. Although entotic cells are internalized while alive, most eventually undergo a non-apoptotic form of cell death, called entotic cell death, that is executed non-cell-autonomously by autophagy proteins and lysosomes. Here we review the current understanding of entosis and entotic cell death and discuss the potential roles of this process in cancer.

Sequential delivery of BMP-2 and BMP-7 for bone regeneration using a heparinized collagen membrane.

To investigate the effect of the sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 on bone regeneration in rat calvarial defects (40 Sprague-Dawley rats, 8mm defect size), all animals were treated with a hydroxyapatite (HA)/tricalcium phosphate (TCP) bone graft covered with a collagen membrane. The experimental groups were as follows: (1) control group: unmodified collagen (no treatment); (2) BMP-2 group: 5 µg of BMP-2; (3) hep-BMP-7 group: 5 µg BMP-7 chemically bound to heparinized collagen; and (4) BMP-2/hep-BMP-7 group: 2.5 µg BMP-7 bound to heparinized collagen and subsequently treated with 2.5 µg BMP-2. Defect healing was examined at 2 and 8 weeks after surgery. The BMP-2 group showed the largest new bone area at week 2 (29.3 ± 7.3%; P = 0.009); new bone areas in the hep-BMP-7 and BMP-2/hep-BMP-7 groups were similar (11.8 ± 3.4% and 12.9 ± 5.71%, respectively; P = 0.917). After 8 weeks, the BMP-2/hep-BMP-7 group showed the largest new bone area (43.3 ± 6.2%), followed by the BMP-2 and hep-BMP-7 groups (P = 0.013). Accordingly, in comparison with single deliveries of BMP-2 and BMP-7, sequential delivery of BMP-2 and BMP-7 using a heparinized collagen membrane significantly induced new bone formation with a smaller quantity of BMP-2 in rat calvarial defects.

Management of an infected cementless cup with prosthetic retention and antibiotic therapy in a dog.

A two-year-old Rottweiler presented for acute onset of a right hindlimb lameness 20 weeks after a cementless total hip replacement (THR) and 16 weeks after open reduction to address luxation of the THR. Radiographs revealed periosteal proliferation of the medial acetabulum and a stable implant. Synovial fluid cytology was consistent with inflammatory joint fluid. Treatment consisted of surgical debridement and intravenous and oral antibiotics. THR implants were not removed. Culture of tissue removed from the THR site yielded growth of Pseudomonas and Staphylococcus species. Lameness resolved 2 months after surgery. Twenty months after surgery, the dog was exercising normally with no clinical lameness and pelvic radiographs revealed no evidence of implant loosening and markedly decreased periosteal reaction. To the authors' knowledge, this is the first report of an infected THR site successfully treated without prosthesis explantation in the dog.

Corrective osteotomy for procurvatum deformity caused by distal femoral physeal fracture malunion stabilised with String-of-Pearls locking plates: results in two dogs and a review of the literature.

BACKGROUND: This report describes the treatment of severe procurvatum because of distal femoral physeal fracture malunion in two skeletally immature dogs. CASE REPORTS: Both dogs presented with severe right hindlimb lameness and markedly reduced stifle extension at less than 5 months of age. Severe distal femoral procurvatum and mild-to-moderate femoral shortening secondary to distal femoral physeal fracture malunion were evident on radiographs. The sagittal plane deformities were addressed with a caudal opening-wedge osteotomy in one dog and cranial closing wedge ostectomy in the other dog. String-of-Pearls locking plates were used to stabilise the osteotomies. Functional stifle extension range of motion and femoral length were improved post surgery in both dogs. Explantation of the plates was required in both dogs because of local soft tissue irritation. Both dogs had excellent outcomes based on subjective and objective measures (pressure sensitive walkway, force platform analysis) when assessed at skeletal maturity. CONCLUSIONS: Corrective osteotomy stabilised with String-of-Pearls locking plates is a viable treatment option for improving limb function in dogs with severe procurvatum deformities caused by distal femoral physeal fracture malunion.

Arthroscopic-guided ulnar distraction for the correction of elbow incongruency in four dogs.

Four skeletally immature, small breed dogs (five elbows) with elbow incongruency were evaluated for forelimb lameness. Findings on clinical examination included pain, effusion and decreased range of motion of the affected elbow. Radiography, computed tomography and arthroscopy demonstrated elbow incongruency in all dogs. Fragmented medial coronoid process was diagnosed arthroscopically in three dogs (four elbows). Arthroscopic subtotal coronoidectomy was performed in all cases of fragmented medial coronoid process. Incongruency was corrected with acute ulnar lengthening under arthroscopic visualisation. The ulna was stabilised with a plate following correction. In two elbows an ostectomy of the anconeal process was performed to prevent impingement against the olecranon fossa. All dogs demonstrated improvement in lameness scores and client-scored visual analogue scale scores. Postoperative computed tomography showed significant improvement in elbow incongruency in all dogs. Arthroscopic-guided ulnar lengthening may be considered as a valid treatment in severe cases of elbow incongruency.

γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate.

BACKGROUND: γ-Glutamyl hydrolase (GGH) regulates intracellular folate and antifolates for optimal nucleotide biosynthesis and antifolate-induced cytotoxicity, respectively. The modulation of GGH may therefore affect chemosensitivity of cancer cells, and exogenous folate levels may further modify this effect. METHODS: We generated a novel model of GGH modulation in human HCT116 and MDA-MB-435 cancer cells and investigated the effect of GGH modulation on chemosensitivity to 5-fluorouracil (5FU) and methotrexate (MTX) at different folate concentrations in vitro and in vivo. RESULTS: Overexpression of GGH significantly decreased chemosensitivity of MDA-MB-435 cells to 5FU and MTX at all folate concentrations as expected. In contrast, in HCT116 cells this predicted effect was observed only at very high folate concentration, and as the folate concentration decreased this effect became null or paradoxically increased. This in vitro observation was confirmed in vivo. Inhibition of GGH significantly increased chemosensitivity of both cancer cells to 5FU at all folate concentrations. Unexpectedly, GGH inhibition significantly decreased chemosensitivity of both cancer cells to MTX at all folate concentrations. In both GGH modulation systems and cell lines, the magnitude of chemosensitivity effect incrementally increased as folate concentration increased. CONCLUSION: Modulation of GGH affects chemosensitivity of cancer cells to 5FU and MTX, and exogenous folate levels can further modify the effects.

The role of protein kinase CK2 in cyclosporine-induced nephropathy in rats.

OBJECTIVES: Protein kinase casein kinase II (PKCK2) has multiple, overlapping roles in induction of apoptosis. Apoptosis can be a common pathway of renal injury caused by a nephrotoxic drug or an injury. We evaluated the role of PKCK2 in cyclosporine (CsA)-induced nephropathy in rats by inhibiting PKCK2 with emodin. METHODS: Male Sprague-Dawley rats fed a low-sodium diet were divided into four treatment groups: control (0.9% saline injection), CsA (15 mg/kg/d subcutaneously), CsA + emodin (CsA plus emodin 20 mg/kg/d subcutaneously), and emodin only. The expression levels of apoptosis-associated factors and of PKCK2 were examined by Western blot analysis. RESULTS: Overexpression of PKCK2 noted with CsA treatment was prevented by emodin, a low-molecular-weight PKCK2 inhibitor, which dampend drug-induced up-regulation phosphorylated p53 and activation of caspases 3, 7, and 8. In addition, emodin prevented increased Bax/Bcl-2 ratio induced by CsA. Emodin prevented up-regulation of PKCK2 by CsA treatment, suggesting that its apoptotic-preventing activity was mediated via PKCK2. CONCLUSIONS: Our findings indicated that PKCK2 may play a role in apoptotic injury associated with CsA-induced nephropathy in rats.

Clinical outcomes and risk factors of post-polypectomy coagulation syndrome: a multicenter, retrospective, case-control study.

BACKGROUND AND STUDY AIMS: Post-polypectomy coagulation syndrome (PPCS) is a well known complication of colonoscopic polypectomy. However, no previous studies have reported on the clinical outcomes or risk factors of PPCS. The aim of the current study was to analyze the clinical outcomes and risk factors of PPCS developing after a colonoscopic polypectomy. PATIENTS AND METHODS: Data for all patients who underwent colonoscopic polypectomies and required hospitalization in nine university hospitals were analyzed retrospectively. The incidence, clinicopathological characteristics, and clinical outcomes of PPCS cases were examined. Additionally, patients who developed PPCS were compared with controls who were matched by age and sex, in order to assess for possible risk factors. RESULTS: The rate of PPCS that required hospitalization after colonoscopic polypectomy was 0.7/1000. All patients with PPCS were treated medically without the need for surgical interventions. The median durations of therapeutic fasting, hospitalization, and antibiotic use were 3 days, 5.5 days, and 7 days, respectively. The rates of major PPCS and mortality were 2.9 % and 0 %, respectively. On multivariate analysis, hypertension (OR = 3.023, 95 %CI 1.034 - 8.832), large lesion size (OR = 2.855, 95 %CI 1.027 - 7.937), and non-polypoid configuration (OR = 3.332, 95 %CI 1.029 - 10.791) were found to be independent risk factors related to the development of PPCS. CONCLUSIONS: In this study, the rates of major PPCS and mortality were only 2.9 % and 0 %, respectively. Hypertension, large lesion size, and non-polypoid configuration of the lesion were independently associated with PPCS. Therefore, patients may be reassured by the excellent prognosis of PPCS, while endoscopists should be especially careful when performing colonoscopic polypectomies in patients with hypertension or large and non-polypoid lesions.

Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

BACKGROUND: Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue syndrome are known as functional pain syndromes. They commonly coexist within the same individual. The pathophysiologic mechanisms of these disorders are not well understood, but it has been hypothesized that they share a common pathogenesis. PURPOSE: The objective of this review is to discuss the proposed pathophysiologic mechanisms, which have been similarly studied in these conditions. These mechanisms include enhanced pain perception, altered regional brain activation, infectious etiologies, dysregulations in immune and neuroendocrine function, and genetic susceptibility. Studies suggest that these functional disorders are multifactorial, but factors which increase the vulnerability of developing these conditions are shared.