Photobacterium damsela (formerly Vibrio damsela) is a pathogen found in both immunocompromised and healthy hosts. It can cause rapid, fulminate infections, such as septicemia, and is associated with a high death rate. Infections generally result from the exposure of subcutaneous tissue to contaminated seawater or from fish-fin puncture wounds [1]. The pathogen can also be transmitted through water or food [2,3]. Here, we discuss the case of a patient with liver cirrhosis who, following his consumption of raw seafood, developed P. damsela septicemia that subsequently resulted in fatal hepatic dysfunction.A 46-year-old man was admitted to our hospital with a 1-day history of fever, abdominal pain, and dyspnea. He had been diagnosed with Child-Pugh Class B alcoholic cirrhosis 2 years prior to presentation and had not consumed alcohol for the last year. The patient had eaten marinated raw fish the day before the symptoms started. On physical examination, his blood pressure was 110/60 mmHg, the pulse rate was 135 beats/min, the respiratory rate was 38/min, and his body temperature was 38.8°C. Abdominal examination revealed diffuse tenderness over the whole abdomen, diminished bowel sounds, and distension. The results of the laboratory tests were: hemoglobin concentration, 9.1 g/dl; leukocyte count, 7,090/l (21% band, 71% poly, 7% lymph); platelet count, 68,000/l; serum creatinine level, 2.0 mg/dl; serum bilirubin level, 8.4 mg/dl; serum albumin level, 2.0 g/dl; prothrombin time, 27.7 s. The arterial blood gas analysis showed metabolic acidosis (pH 7.05, pCO 2 17.6 mmHg, pO 2 83.3 mmHg, HCO 3 10 mmol/l). The ascitic fluid analysis revealed an albumin level of 0.3 g/dl and a leukocyte count of 12,050/l (100% poly). Early esophageal varices were observed during an upper gastrointestinal endoscopy. Coarse hepatic parenchymal echogenicity, ascites, and splenomegaly were evident on the abdominal ultrasonograph. Blood cultures were taken within 1 h of admission to hospital. The ascitic fluid was inoculated in aerobic and anaerobic blood culture bottles simultaneously [4].Three days after admission, analysis of the blood cultures using the BACTEC 9240 blood culture system (Becton Dickinson, Sparks, MD, USA) revealed Gramnegative bacilli that were subsequently identified as P. damsela using a VITEK GN card (bioMé rieux, Marcyl'Etoile, France). The phenotypes of this strain were analyzed biochemically using the API 20E test (bio-Mé rieux), as per the manufacturer's instructions. In this test, 20 conventional substrates are inoculated with a 0.85% saline suspension of the organism being tested. O'Hara et al. [5] found that the identification of P. damsela using the API and VITEK GN system was 100% accurate. The strain tested positive for glucose fermentation and the oxidase, urease, and arginine dihydrolase activity tests. The indole test was negative. The MIC of various antimicrobial agents for this isolate was determined by the microbroth dilution method using graded concentrations of antimicrobial agents [6]. This strain was ...
1. Thiols have been implicated to play a role in a variety of aspects of nitric oxide (NO) generation and activity. Thiol dependence of nitric oxide synthase (NOS) has remained controversial and its mechanism is not clear. This study investigates possible mechanisms between thiol (SH group) and NOS activation, through thiol compounds (glutathione, dithiothreitol, N-acetyl-L-cysteine) and Ebselen [2-phenyl-1,2-benzisoselenazole-3(2H)-one] on rat aortic vascular responses. 2. In rat thoracic aorta, acetylcholine (10(-6)-10(-9) M) induced a relaxation of phenylephrine (PE) (10(-7) M)-induced tone, which was inhibited dose dependently by increasing concentration of ebselen (1-10 microM). 3. In rings of rat thoracic aorta, ebselen and NOS inhibitors (NG-monomethyl-L-arginine, NG-nitro-L-arginine methyl ester) produced an augmentation of phenylephrine (10(-7) M)- induced tone and acetylcholine induced a relaxation of PE (10(-7) M)-induced tone in rat thoracic aorta, which was inhibited by ebselen (10 microM) like NOS inhibitor. 4. The thiol compounds (glutathione, dithiothreitol, and N-acetyl-L-cysteine) alone did not change vascular tone in rat thoracic aorta. Pretreatment with thiol compounds before ebselen treatment, however, reversed the inhibitory effect of ebselen which acts like the NOS inhibitor in rat thoracic aorta. Posttreatment with thiol compounds after ebselen treatment did not reverse the inhibitory effect of ebselen by as much as pretreatment. 5. Calcium ionophore A23187 (10(-7) M)-induced vasodilation was inhibited in ebselen pretreated rat thoracic aorta, but sodium nitroprusside (SNP, 10(-7) M)-induced relaxation was not inhibited by ebselen. This suggests that NOS is involved in the inhibitory effect of ebselen on rat thoracic aorta relaxation. 6. These results suggest that ebselen exerts an inhibitory action on the nitric oxide synthesis in rat thoracic aorta by interacting with thiol groups.
Background: Programmed death ligand 1 (PD-L1), a potential target for immune checkpoint inhibitors, has been considered a novel biomarker for prognosis in various solid tumors. However, scant data is available on the role of PD-L1 expression in advanced gallbladder cancer (GBC). The aim of this study is to evaluate prognostic significance of expression of PD-L1 in advanced GBC and provide evidence for PD-L1 targeted therapy in the future. Methods: We investigated the expression of PD-L1 in 192 advanced GBC cases who underwent surgery and were pathologically confirmed as T3 or T4 between 2010 and 2017. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Clinicopathological characteristics and survival data were correlated with PD-L1 expression analyzed at different cut-offs of ≥ 1%, ≥ 10% and ≥ 50% in tumor cells and tumor-infiltrating immune cells. Results: Tumor cells expressed PD-L1 in 47.4% of cases (n = 91), and tumor-infiltrating immune cells expressed PD-L1 in 70.5% of cases (n = 135). The median overall survival (OS) and median progression-free survival (PFS) of patients with PD-L1 positivity in tumor-infiltrating immune cells at a cutoff of 10% was 23.9 and 16.8 months, respectively and significantly better than those of patients with PD-L1 negativity (23.9 vs. 15.7 months, p = 0.023, 16.8 vs. 10.0 months, p = 0.018). In multivariate analysis, simple cholecystectomy, no adjuvant chemotherapy and PD-L1 negativity (negative & < 10% positive) in tumor-infiltrating immune cells were significant poor prognostic factors. Conclusions: Our results showed that PD-L1 expression in tumor-infiltrating immune cells at a cutoff of 10% is an independent significant prognostic factor in advanced GBC patients. Therefore, PD-L1 expression could be a good prognostic marker to guide future immune target-based therapies in GBC. Further large scale study is needed.
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