Beneficial effects of bardoxolone methyl, an Nrf2 activator, on crush-related acute kidney injury in rats.

PURPOSE: The purpose of this study was to investigate the effects of bardoxolone methyl (BM), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, on acute kidney injury in a rat model of crush syndrome model. METHODS: Sixty-four rats were separated equally into eight groups, sham (sterile saline ip), crush, crush + vehicle (DMSO ip), and crush + BM (10 mg/kg ip) (n = 8). All groups were also divided as 3 and 24 h after decompression. Crush injury was induced by 6 h of direct compression to both hind limbs of the rats with blocks weighing 3.6 kg on each side, followed by 3 and 24 h of decompression. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrotizing factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1) concentrations, tissue total oxidant status (TOS) and total antioxidant status (TAS) were measured in the kidneys. Serum creatine kinase (CK), blood urea nitrogen (BUN) and creatinine concentrations were also measured. Glomerular and tubular structures were examined histopathologically. Bcl-2 was measured using immunohistochemistry. Apoptosis was assessed using the TUNEL method. RESULTS: BM treatment reduced KIM-1, NGAL, TNF-α, TGF-ß1, TOS concentrations, and increased TAS concentrations in the kidneys 3 and 24 h after decompression. Serum CK, BUN and creatinine concentrations were also reduced with BM. BM treatment decreased apoptosis in crush-related AKI. The Nrf2 activator BM reversed the crush-induced changes in the experimental rats. CONCLUSION: BM treatment prevented the progression of crush-related AKI in rats possibly through its cytoprotective effects of being an antioxidant, anti-inflammatory and anti-apoptotic agent.

Effect of Hydrogen Sulfide on Kidney Injury in Rat Model of Crush Syndrome.

BACKGROUND: Acute kidney injury is the most serious complication of crush syndrome. Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule. It is involved in homeostatic functions, such as blood pressure control, apoptosis, oxidative stress, and inflammation. In this study, effects of H2S on kidney injury were investigated in a rat model of crush syndrome. METHODS: Rats were divided into six groups (n = 8): Sham (steril saline ip), crush (sterile saline ip), crush + NaHS (sodium hydrosulfide, an H2S donor) (100 µmol/kg ip). All these groups were also separated as 3 and 24 h after decompression. Crush injury was induced by 6 h of direct compression to both hindlimbs of anesthetized rats with blocks weighing 3.6 kg each sides, followed by 3 or 24 h of decompression. Kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, tumor-necrotizing factor-α, transforming growth factor-ß, tissue total oxidant status, and total antioxidant status levels were measured in kidney homogenates 3 and 24 h after decompression. Serum creatine kinase, blood urea nitrogen, and creatinine levels were also measured. Apoptosis was assessed by TUNEL method. Bcl-2 was assessed by immunohistochemistry. Glomerular and tubular structures were also examined histopathologically. RESULTS: NaHS reduced kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, tumor-necrotizing factor-α, transforming growth factor-ß, total oxidant status levels, and increased total antioxidant status levels in kidney 3 and 24 h after decompression. Serum urea, creatinine, and creatine kinase levels also reduced with NaHS. NaHS decreased renal damage and apoptosis in crush-related acute kidney injury. CONCLUSIONS: These results suggest that H2S could reduce crush-related acute kidney injury via anti-inflammatory, antioxidant, and antiapoptotic effects.

Myxoglobulosis in the appendix.

Myxoglobulosis is a specific type of mucocele consisting of mucoid material. It is characterized by opaque, transparent globules that resemble "fish eggs" or "frogspawns". It is generally diagnosed incidentally during an appendectomy or an autopsy. In this paper, we aim to present the case of a 58-year-old male patient who was referred to our hospital because of abdominal pain and loss of appetite. The patient underwent an appendectomy. Opaque intraluminal globules were found in the appendectomy material. The globules resembled pearls and they were 2-3 mm in diameter. After histopathological examinations, the patient was diagnosed with myxoglobulosis accompanied with acute appendicitis. According to our research, this is the first case of myxoglobulosis in our country.

A massive update of non-indigenous species records in Mediterranean marinas.

The Mediterranean Sea is home to over 2/3 of the world's charter boat traffic and hosts an estimated 1.5 million recreational boats. Studies elsewhere have demonstrated marinas as important hubs for the stepping-stone transfer of non-indigenous species (NIS), but these unique anthropogenic, and typically artificial habitats have largely gone overlooked in the Mediterranean as sources of NIS hot-spots. From April 2015 to November 2016, 34 marinas were sampled across the following Mediterranean countries: Spain, France, Italy, Malta, Greece, Turkey and Cyprus to investigate the NIS presence and richness in the specialized hard substrate material of these marina habitats. All macroinvertebrate taxa were collected and identified. Additionally, fouling samples were collected from approximately 600 boat-hulls from 25 of these marinas to determine if boats host diverse NIS not present in the marina. Here, we present data revealing that Mediterranean marinas indeed act as major hubs for the transfer of marine NIS, and we also provide evidence that recreational boats act as effective vectors of spread. From this wide-ranging geographical study, we report here numerous new NIS records at the basin, subregional, country and locality level. At the basin level, we report three NIS new to the Mediterranean Sea (Achelia sawayai sensu lato, Aorides longimerus, Cymodoce aff. fuscina), and the re-appearance of two NIS previously known but currently considered extinct in the Mediterranean (Bemlos leptocheirus, Saccostrea glomerata). We also compellingly update the distributions of many NIS in the Mediterranean Sea showing some recent spreading; we provide details for 11 new subregional records for NIS (Watersipora arcuata, Hydroides brachyacantha sensu lato and Saccostrea glomerata now present in the Western Mediterranean; Symplegma brakenhielmi, Stenothoe georgiana, Spirobranchus tertaceros sensu lato, Dendostrea folium sensu lato and Parasmittina egyptiaca now present in the Central Mediterranean, and W. arcuata, Bemlos leptocheirus and Dyspanopeus sayi in the Eastern Mediterranean). We also report 51 new NIS country records from recreational marinas: 12 for Malta, 10 for Cyprus, nine for Greece, six for Spain and France, five for Turkey and three for Italy, representing 32 species. Finally, we report 20 new NIS records (representing 17 species) found on recreational boat-hulls (mobile habitats), not yet found in the same marina, or in most cases, even the country. For each new NIS record, their native origin and global and Mediterranean distributions are provided, along with details of the new record. Additionally, taxonomic characters used for identification and photos of the specimens are also provided. These new NIS records should now be added to the relevant NIS databases compiled by several entities. Records of uncertain identity are also discussed, to assess the probability of valid non-indigenous status.

Correction: A massive update of non-indigenous species records in Mediterranean marinas.

[This corrects the article DOI: 10.7717/peerj.3954.].

Bridge treatment for early cholecystectomy in geriatric patients with acute cholecystitis: Percutaneous cholecystostomy.

BACKGROUND: The main cause of acute cholecystitis (AC) is gallstones, and the incidence of gallstones in elderly patients is high. METHODS: In this study, we aimed to investigate the efficacy of percutaneous cholecystostomy (PC) before early cholecystectomy in geriatric patients with AC. This retrospective study included 85 patients undergoing laparoscopic or conventional cholecystectomy during early stage of calculous AC. RESULTS: All patients were over 65 years old and were divided into two groups: Group I, PC plus early cholecystectomy and Group II, only cholecystectomy without PC. Data on age, sex, status of PC before surgery, postoperative complications, postoperative mortality, surgical method, and postoperative hospitalization duration were recorded in our study. The average age in the groups I and II was 75.7±7.5 and 73.7±7.2 years, respectively, indicating insignificant difference (p=0.223). Although postoperative complication rate was two fold in the non-PC group, the PC plus cholecystectomy group has a few complications (p=0.032). Postoperative mortality was evidently lower in patients who first underwent PC and followed by cholecystectomy (p=0.017). The average hospitalization duration in groups I and II were 5.6±2.4 days and 11.2±7.7 days, respectively (p<0.001). CONCLUSION: Urgent laparoscopic cholecystectomy is still the best surgical treatment modality for calculous AC. Further, our study results showed that in geriatric patients, bridge treatment, such as PC, can be useful for reducing postoperative complication rates.

Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model.

Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. RESULTS: Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. CONCLUSIONS: These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

MicroRNA-125b as a new potential biomarker on diagnosis of renal ischemia-reperfusion injury.

BACKGROUND: Acute renal failure is commonly seen in the perioperative period. Ischemia-reperfusion (IR) injury plays a major role in acute renal failure and delayed graft function. MicroRNAs (miRs), which are pivotal modulators of cell activities, offer a major opportunity for affective diagnosis and treatment strategies because they are tissue specific and in the center of gene expression modulation. The effect of bardoxolone methyl (BM) on miR-21, miR-223-5p, and miR-125b in renal IR injury was evaluated in this study. METHODS: Wistar-Albino rats (12-16 wk old, weighing 300-350 g) were used in the study. Rats (n = 6) were randomized into three groups (control, IR, and BM + IR). Tissue levels of miRs were analyzed with reverse transcription polymerase chain reaction. RESULTS: Significant reduction of urea and total oxidant status, increase of total antioxidant status, and oxidative stress index were identified in the IR + BM group compared with the IR group. Significant increases of miR-21 (2842.82-fold) and miR-125b (536.8-fold) were identified in the IR group compared with the control group; however, miR-223-5p levels did not show any significant difference. Also, miR-21 and miR-125b were significantly reduced in the IR + BM group compared with the IR group. Reduced histopathologic changes were observed in the IR + BM group. A significant decrease in the number of tunel-positive cells was identified in the IR + BM group compared with the IR group. CONCLUSIONS: miR-125b was significantly increased in IR injury; thus, miR-125b can be a potential novel marker that can be used in diagnosis and treatment of renal IR injury. BM reduces miR-21 and miR-125b in case of IR injury and makes functional and histopathologic repairs.

Prolidase activity and oxidative stress in patients with breast carcinoma A prospective randomized case-controlled study.

INTRODUCTION: Oxidative stress plays an important role in the pathogenesis of malign diseases. Prolidase is a member of the matrix metalloproteinase family, plays a major role in collagen metabolism, cell growth, and matrix remodeling. Elevated serum prolidase activity have beendemonstrated in several types of carcinoma. The aim of this study is to investigate the serum prolidase activity, total oxidant status (TOS), total antioxidant status (TAS) and to evaluate their relationship with tumor stage, lymph node metastasis, and tumor size in patients with breast carcinoma. METHODS: Thirty-five patients with breast carcinoma and forty healthy controls were enrolled to this study.Serum TAS, TOS levels, and prolidase activities were measured and oxidative stress indices (OSI) were calculated. RESULTS: TOS, OSI levels and prolidase activities were significantly higher in the patients with breast carcinoma compared to the control group (P < 0.001, P < 0.001, P = 0.002, respectively).TAS levels were significantly lower in the in the patients with breast carcinoma compared to the control group (P = 0.016).Positive correlations were found between prolidase activity, TOS, OSI levels and tumor stage, lymph node metastasis, and tumor size. A negative correlation was found between TAS levels and tumor size,hovewer there were no correlationsbetween tas levels and stage of the tumor,as well as lymph node infiltration. CONCLUSION: We conclude that elevatedserum prolidase activity and oxidative stress may be associated with breast carcinoma. Increased serum prolidase activity may be related to stage and prognosis of breast carcinoma. KEY WORDS: Breast carcinoma, Oxidative stress, Proline dipeptidase.

Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion.

AIM: MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model. METHODS: We used 12-16 weeks-old Wistar-Albino rats that weigh 300-350 g. Rats (n, 6) were randomized into four groups (Control, IR, IR + CAP, IR + TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed. RESULTS: Urea, creatinine, TOS, OSI levels of IR + CAP, and IR + TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR + TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR + CAP and IR + TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR + CAP and IR + T groups than IR group. CONCLUSION: We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.

Gastroprotective effects of sulforaphane and thymoquinone against acetylsalicylic acid-induced gastric ulcer in rats.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly cause gastric ulcers (GUs). We investigated the effects of sulforaphane (SF) and thymoquinone (TQ) in rats with acetylsalicylic acid (ASA)-induced GUs. MATERIALS AND METHODS: Thirty-five male Wistar-Albino rats were divided into five groups: control; ASA; ASA with vehicle; ASA + SF; and ASA + TQ. Compounds were administered by oral gavage before GU induction. GUs were induced by intragastric administration of ASA. Four hours after GU induction, rats were killed and stomachs excised. Total oxidant status, total antioxidant status, total thiol, nitric oxide, asymmetric dimethylarginine, tumor necrosis factor-alpha levels, superoxide dismutase activity, and glutathione peroxidase activity in tissue were measured. Messenger RNA expression of dimethylarginine dimethylaminohydrolases, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells were analyzed. Renal tissues were evaluated by histopathologic and immunohistochemical means. RESULTS: SF and TQ reduced GU indices, apoptosis, total oxidant status, asymmetric dimethylarginine, and tumor necrosis factor-alpha levels, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase expressions (P < 0.001, P = 0.001). Both examined compounds increased superoxide dismutase activity, glutathione peroxidase activity, total antioxidant status, total thiol, nitric oxide levels, endothelial nitric oxide synthase, dimethylarginine dimethylaminohydrolases, HO-1, nuclear factor erythroid 2-related factor 2, and HO-1 expressions (P < 0.001). CONCLUSIONS: These results suggest that pretreatment with SF or TQ can reduce ASA-induced GUs via anti-inflammatory, antioxidant, and antiapoptotic effects. These compounds may be useful therapeutic strategies to prevent the gastrointestinal adverse effects that limit nonsteroidal anti-inflammatory drugs use.

DOES NEUTROPHIL TO LYMPHOCYTE RATIO PREDICT HOSPITAL STAY IN APPENDECTOMY PATIENTS?

BACKGROUND: We aimed to investigate the relationship between the neutrophil to lymphocyte ratio (NLR) and postoperative length of hospital stay. In addition, the impact of radiological and histopathological findings on hospital stay was also evaluated. METHOD: This is a retrospective study. One hundred three patients with appendicitis were in-cluded. The diagnosis was confirmed by computed tomography (CT), ultrasonography and histopathological examination. Correlations between the length of hospital stay and age, gender, NLR, c-reactive peptide levels (CRP), the appendix diameter on CT or ultrasonogra-phy, appendix localisation and pathology reports were evaluated. RESULTS: The length of hospital stay was not related to age or gender. The length of hospital stay after appendectomy was correlated with appendix diameter on CT and phlegmonous appendicitis, but it was not associated with NLR, CRP levels or the appendix diameter on ultrasonography. CONCLUSION: To our knowledge, this is the first comprehensive study to evaluate the associa-tion between NLR levels and the length of hospital stay in patients with acute appendicitis. The NLR was not found to be associated with the length of hospital stay. The appendix di-ameter on CT and appendix pathology reports were correlated with the length of postopera-tive hospital stay in appendectomy patients.

Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model.

BACKGROUND: Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory agent. We investigated the protective effect of PF against postoperative intra-abdominal adhesions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were divided into three groups (n = 10 in each group). In group 1 (control), adhesion induction was performed by cecal abrasion, and no treatment was administered. In group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose was administered by gavage. In group 3 (PF treatment), for 2 wk after adhesion induction, 500-mg/kg/d PF was administered by gavage. On the 15th postoperative day, the animals were killed, and cecal and peritoneal tissues were excised. The adhesions were graded macroscopically. The protein concentrations and mRNA expression levels of the following genes were measured in the tissues: matrix metallopeptidase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1); tumor necrosis factor-alpha (TNF-α); and transforming growth factor-beta 1 (TGF-ß1). The tissue samples were also evaluated histopathologically. RESULTS: Macroscopic and histopathologic evaluation showed that PF-reduced adhesion and inflammation (P < 0.001, P = 0.004, respectively). Pretreatment with PF-reduced TIMP-1, TNF-α, and TGF-ß1 protein concentrations (P < 0.001, P < 0.001, and P < 0.001, respectively) and mRNA expression levels (P = 0.030, P = 0.005, and P = 0.016, respectively) and increased MMP-9 protein concentrations (P < 0.001) and mRNA expression (P = 0.021). CONCLUSIONS: The findings of this study suggest that PF can be used as a protective agent to prevent the development of peritoneal adhesions and inflammation during the postoperative period.

Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats.

AIMS: Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS: Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-α (TNF-α) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-κB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically. KEY FINDINGS: All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF-α levels, NF-κB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH-Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions. SIGNIFICANCE: Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects.

Ukrain (NSC 631570) ameliorates intestinal ischemia-reperfusion-induced acute lung injury by reducing oxidative stress.

Intestinal ischemia-reperfusion (I/R) causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570) is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L.) plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS), total antioxidant status (TAS) were measured and oxidative stress indices (OSI) were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05). TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05). Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed  in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05). Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects.

Incidental signet ring cell carcinoma of the gallbladder in routine histopathology.

Cholecystectomy is a common surgical procedure for various indications. Preoperative imaging is the main stay in the management of the patients. Routine and/or selective histopathological examination of the cholecystectomy materials have been discussed previously. However, incidental findings may be only observed with routine histopathological examination. Here, we report an incidental gallbladder signet cell carcinoma in a 66 years old patient. This case underlines the importance of routine histopathological examination after cholecystectomy.

Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.

Renal ischemia-reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar-Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60-min ischemia and a 120-min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator-activated receptor-É£ (PPAR-É£), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF-κB, inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH-Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR-É£ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti-inflammatory, antioxidant and anti-apoptotic effects.

An Uncommon Side Effect of Bupropion: A Case of Acute Generalized Exanthematous Pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a rare inflammatory dermatosis characterized by multiple nonfollicular pustules that occur on erythematous skin. Despite its similarity to pustular psoriasis and association with fever and leukocytosis, AGEP typically heals quickly. Etiologically, drugs and viruses have been suspected in most cases. Here, we present a case of AGEP, in a woman, that developed 1 day after starting bupropion for smoking cessation, as a rare side effect of the treatment.

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (p<0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (p<0.01, p<0.05, respectively), and increased SOD, GPx, and CAT activities (p<0.001, p<0.01, p<0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (p<0.01, p<0.05, p<0.001) and MDA and NO levels (p<0.05, p<0.01) and decreased SOD, GPx, and CAT activities (p<0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

A case of scar sarcoidosis developing in an old scar area on the forehead.

Sarcoidosis is a multisystem disease characterized by noncaseating granuloma development. Scar sarcoidosis is a rare cutaneous form of sarcoidosis developing on previous cutaneous scar areas. The lesions may be solitary or occur along with systemic disease. We present the case of a female patient that developed cutaneous sarcoidosis in an old scar area on the forehead that was acquired 30 years ago due to injuries from a fall. Histopathological examinations of the excisional scar biopsy revealed non-necrotizing, noncaseating granulomatous inflammatory structures comprised of epithelioid cells and Langhans giant cells with lymphocytic infiltration within the reticular dermis consistent with sarcoidosis. High-resolution CT revealed bilateral mediastinal lymphadenopathy. Patients with inflammatory skin lesions at the sites of preexisting scars should be investigated for sarcoidosis. Histopathological examination of skin biopsy specimens usually provides the correct and final diagnosis.