18-Fluorodeoxyglucose Positron Emission Tomography Predicts Recurrence in Resected Pancreatic Ductal Adenocarcinoma

Background

We aimed to determine whether treatment should be stratified according to 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) maximum standardized uptake values (SUV_max) in pancreatic ductal adenocarcinoma.

Methods

Patients who underwent preoperative 18F-FDG PET/CT between 2006 and 2014 (n = 138) were stratified into high (≥ 4.85) and low (< 4.85) PET groups. The clinicopathological characteristics and prognostic outcomes were analyzed retrospectively.

Results

The primary tumor SUV_max was positively correlated with preoperative CA19-9 levels (P < 0.001). The high PET group failed to achieve postoperative CA19-9 normalization (P = 0.014). Disease-specific (P < 0.001), recurrence-free (P < 0.001), liver recurrence-free (P < 0.001), and peritoneal recurrence-free (P = 0.020) survivals were significantly shorter in the high PET group. The primary tumor SUV_max was an independent predictive risk factor for liver metastasis (hazard ratio 3.46, 95% confidence interval 1.61–7.87; P = 0.001) and peritoneal recurrence (hazard ratio 3.36, 95% confidence interval 1.18–10.89; P = 0.023).

Conclusions

Surgical resection failed to achieve CA19-9 normalization in the high PET group and distant recurrence was frequent. This suggests the potential for residual cancer at distant sites, even after curative resection. Stronger preoperative systemic chemotherapy is preferred for the high PET group patients.

     

Pre-transfusion screening for platelet-reactive antibodies.

We retrospectively compared the cost of platelet concentrates (PCs) used for patients whose serum had already been screened for platelet-reactive antibodies with the cost for patients whose serum was examined after the commencement of treatment using platelets. On the basis of 774 patients' data, the mean cost of PCs for the latter group of patients ($5562) was higher than that for the former group ($2547). Screening beforehand ensured a prompt supply of specific PCs, and costs were suppressed by the avoidance of multiple transfusions. We conclude that screening for platelet-reactive antibodies followed by administration of crossmatch-negative PCs appears to be both clinically and economically advantageous.     

Genetic and antigenic characterization of H5 and H7 avian influenza viruses isolated from migratory waterfowl in Mongolia from 2017 to 2019

Virus Genes - The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public...     

Further characterization of reversal of signs of induced cotton effects of dicumarol derivatives-alpha 1-acid glycoprotein systems by protriptyline.

The interaction of dicumarol derivatives and protriptyline with respect to the binding to alpha 1-acid glycoprotein (AGP) has been investigated by circular dichroism (CD), equilibrium dialysis and ultrafiltration. Investigation of the induced CD spectra of dicumarol derivatives bound to AGP indicated that the conformations of these compounds were different when bound to AGP. Though all the dicumarol derivatives, protriptyline and AGP formed a ternary complex, interaction modes were different, depending upon the substituent groups at position 3 of the dicumarol molecule. On the basis of the protriptyline effect on the CD spectra of all dicumarol derivatives bound to AGP, the compounds were classified in the following way: (1) Dicumarol, ethylidenebis 4-hydroxycoumarin and propylidenebis 4-hydroxycoumarin caused reversal of the sign of ellipticity. This interaction was explained by cooperative binding. (2) Butylidenebis 4-hydroxycoumarin and pentylidenebis 4-hydroxycoumarin generated new band and disappeared ellipticity of the original Cotton effect. This interaction was also explained by the cooperative binding mode. (3) Ethylbiscoumacetate which generated the CD band similar to that of dicumarol in the absence of protriptyline, reversed the sign of the CD spectrum only at 325 nm. The interaction was anticooperative in nature. (4) Benzylidenebis 4-hydroxycoumarin represented type four which had no change in the CD spectrum by the addition of protriptyline. This interaction was explained by the two-state model accompanying the conformational change of AGP. These results suggested that all compounds, except for benzylidenebis 4-hydroxycoumarin, induced negative Cotton effects at 325 nm by taking the same asymmetrical perturbation by the addition of protriptyline and the interaction was carried out according to model 2. An attempt to study the interaction mechanism of two or more drugs with regard to the binding to protein using these models is thought to help in understanding drug-protein interactions.     

Characterization of uremic toxin transport by organic anion transporters in the kidney

BACKGROUND: Harmful uremic toxins, such as indoxyl sulfate (IS), 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), indoleacetate (IA), and hippurate (HA), accumulate to a high degree in uremic plasma. IS has been shown to be a substrate of rat organic anion transporter 1 (rOat1) and rOat3. However, the contribution of rOat1 and rOat3 to the renal uptake transport process of IS and other uremic toxins in the kidney remains unknown. METHODS: The cellular uptake of uremic toxins was determined using stable transfectants of rOat1/hOAT1 and rOat3/hOAT3 cells. Also, the uptake of uremic toxins by rat kidney slices was characterized to evaluate the contribution of rOat1 and rOat3 to the total uptake by kidney slices using inhibitors of rOat1 (p-aminohippurate) and rOat3 (pravastatin and benzylpenicillin). RESULTS: Saturable uptake of IS, CMPF, IA, and HA by rOat1 was observed with Km values of 18, 154, 47, and 28 micromol/L, respectively, whereas significant uptake of IS and CMPF, but not of IA or HA, was observed in rOat3-expressing cells with Km values of 174 and 11 micromol/L, respectively. Similar parameters were obtained for human OAT1 and OAT3. Kinetic analysis of the IS uptake by kidney slices revealed involvement of two saturable components with Km1 (24 micromol/L) and Km2 (196 micromol/L) values that were comparable with those of rOat1 and rOat3. The Km value of CMPF uptake by kidney slices (22 micromol/L) was comparable with that of rOat3, while the corresponding values of IA and HA (42 and 33 micromol/L, respectively) were similar to those of rOat1. PAH preferentially inhibited the uptake of IA and HA by kidney slices, while pravastatin and benzylpenicillin preferentially inhibited the uptake of CMPF. The effect of these inhibitors on the uptake of IS by kidney slices was partial. CONCLUSIONS: rOat1/hOAT1 and rOat3/hOAT3 play major roles in the renal uptake of uremic toxins on the basolateral membrane of the proximal tubules. Both OAT1 and OAT3 contribute almost equally to the renal uptake of IS. OAT3 mainly accounts for CMPF uptake by the kidney, while OAT1 mainly accounts for IA and HA uptake.     

Characterization of site I of human serum albumin using spectroscopic analyses: locational relations between regions Ib and Ic of site I

Site I of human serum albumin is an important and complex region for high-affinity binding of drugs. Equilibrium dialysis showed independent binding of dansyl-L-asparagine (DNSA) and n-alkyl p-aminobenzoates (p-ABEs) to regions Ib and Ic, respectively, in the pH range 6.0-9.0. However, individual binding of DNSA increased with pH in the same range. Binding of the four n-alkyl p-ABEs strongly perturbed the circular dichroism spectrum of bound DNSA, and the effect increased with concentration and the number of carbon atoms in the alkyl moiety. A similar effect was observed by increasing pH from 6.0 to 9.0, a pH range in which human serum albumin is known to undergo the neutral-to-base transition. The spectral changes propose spatial orientation changes of DNSA at region Ib. This proposal was supported by increased fluorescence anisotropy values: n-alkyl p-ABEs binding and the pH-dependent conformational change each restricted the mobility of the naphthalene ring of bound DNSA. Despite the similar effects on the spatial orientation of DNSA, clear differences were observed between the effects of n-alkyl p-ABEs and neutral-to-base transition. The former hardly changed the affinity and maximum fluorescence emission wavelength of bound DNSA; in contrast, the latter significantly affected them. The results give new information about site I and, according to our knowledge, represent a new type of ligand interaction, because the binding site of DNSA could be changed by simultaneous binding of the n-alkyl p-ABEs without affecting the binding constant.