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1.
J Fish Biol ; 103(2): 260-271, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37166994

ABSTRACT

The present study examined body length (precaudal length, PCL) and age at sexual maturity, as well as fecundity and maternal investment in the Pacific spiny dogfish Squalus suckleyi, a long-term commercially exploited shark in the western North Pacific, using samples caught in several fisheries and across seasons. The PCL and age at 50% sexual maturity of males were 60.6 cm and 9.4 years, respectively, and those of females were 73.1 cm and 17.8 years, respectively. The PCL and age at 50% maternity were 77.4 cm and 19.7 years, respectively. General or generalized linear models revealed that capture by different fishing method did not significantly correlate with sexual maturity and maternity rates or litter size. Other general linear models revealed an increase in offspring size with maternal size, but litter size was not affected by embryonic development. These findings indicate that the reproductive potential of Pacific spiny dogfish is relatively high throughout the whole North Pacific region because of a smaller size and earlier age at sexual maturation in both sexes. In addition, pregnant females displayed no resting phase and produced 0.45 more embryos per centimetre of PCL in their lifetime after the onset of maturity, which is higher than in the eastern North Pacific. We suggest that these qualities are not a consequence of stock decline associated with the long-term exploitation of the species, but that its high reproductive potential has likely contributed to the long-term stability of the landings in Japan. SIGNIFICANCE STATEMENT: While reproductive potential has been determined for many fish species, such information is scarce for Pacific spiny dogfish. We evaluated the reproductive characteristics of this species in the major fishing grounds of the western North Pacific. The productivity and rebound potential of sharks is extremely low compared with those of bony fishes. However, our results indicate that even if the reproductive potential has a small effect on the population dynamics, it should not be ignored for sustainable stock utilisation.


Subject(s)
Sharks , Squalus , Pregnancy , Male , Female , Animals , Hunting , Reproduction , Fertility
2.
Eur J Cancer ; 65: 164-71, 2016 09.
Article in English | MEDLINE | ID: mdl-27501505

ABSTRACT

BACKGROUND: Lentinan (LNT) is a purified ß-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment. RESULTS: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group. CONCLUSIONS: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer. CLINICAL TRIAL REGISTRATION ID NUMBER: UMIN 000000574.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lentinan/therapeutic use , Oxonic Acid/therapeutic use , Stomach Neoplasms/drug therapy , Tegafur/therapeutic use , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Drug Combinations , Female , Humans , Male , Middle Aged , Monocytes/metabolism , Quality of Life
3.
Surg Today ; 46(12): 1383-1386, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27017599

ABSTRACT

PURPOSE: To compare the outcomes of laparoscopic surgery vs. open surgery after insertion of a colonic stent for obstructive colorectal cancer. METHODS: Between April 2005 and August 2013, 58 patients underwent surgery after the insertion of a colonic stent for obstructive colorectal cancer. We analyzed the outcomes of the patients who underwent laparoscopic surgery vs. those who underwent open surgery. RESULTS: We compared blood loss, operative time, hospital stay, and complications in 26 patients who underwent laparoscopic surgery and 32 patients who underwent open surgery. Blood loss was significantly less in the laparoscopic surgery group, but operative time was significantly shorter in the open surgery group. The length of hospital stay was shorter in the laparoscopic surgery group than in the open surgery group, but the difference was not significant. There was no significant difference in postoperative surgical complications between the groups. CONCLUSION: The patients who underwent laparoscopic resection had less blood loss, although no significant difference was found in postoperative morbidity or mortality. Thus, laparoscopic resection after stent insertion is a feasible and safe option for patients with obstructive colorectal cancer.


Subject(s)
Colorectal Neoplasms/complications , Colorectal Neoplasms/surgery , Digestive System Surgical Procedures/methods , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Laparoscopy , Stents , Aged , Blood Loss, Surgical/statistics & numerical data , Female , Humans , Length of Stay , Male , Morbidity , Operative Time , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Treatment Outcome
4.
Rev Sci Instrum ; 85(9): 094502, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25273747

ABSTRACT

A pressurized subsampling system was developed for pressured gas hydrate (GH)-bearing sediments, which have been stored under pressure. The system subsamples small amounts of GH sediments from cores (approximately 50 mm in diameter and 300 mm in height) without pressure release to atmospheric conditions. The maximum size of the subsamples is 12.5 mm in diameter and 20 mm in height. Moreover, our system transfers the subsample into a pressure vessel, and seals the pressure vessel by screwing in a plug under hydraulic pressure conditions. In this study, we demonstrated pressurized subsampling from artificial xenon-hydrate sediments and nondestructive microscale imaging of the subsample, using a microfocus X-ray computed tomography (CT) system. In addition, we estimated porosity and hydrate saturation from two-dimensional X-ray CT images of the subsamples.

5.
BMC Genomics ; 15: 233, 2014 Mar 26.
Article in English | MEDLINE | ID: mdl-24669946

ABSTRACT

BACKGROUND: Recent advancements in next-generation sequencing technology have enabled cost-effective sequencing of whole or partial genomes, permitting the discovery and characterization of molecular polymorphisms. Double-digest restriction-site associated DNA sequencing (ddRAD-seq) is a powerful and inexpensive approach to developing numerous single nucleotide polymorphism (SNP) markers and constructing a high-density genetic map. To enrich genomic resources for Japanese eel (Anguilla japonica), we constructed a ddRAD-based genetic map using an Ion Torrent Personal Genome Machine and anchored scaffolds of the current genome assembly to 19 linkage groups of the Japanese eel. Furthermore, we compared the Japanese eel genome with genomes of model fishes to infer the history of genome evolution after the teleost-specific genome duplication. RESULTS: We generated the ddRAD-based linkage map of the Japanese eel, where the maps for female and male spanned 1748.8 cM and 1294.5 cM, respectively, and were arranged into 19 linkage groups. A total of 2,672 SNP markers and 115 Simple Sequence Repeat markers provide anchor points to 1,252 scaffolds covering 151 Mb (13%) of the current genome assembly of the Japanese eel. Comparisons among the Japanese eel, medaka, zebrafish and spotted gar genomes showed highly conserved synteny among teleosts and revealed part of the eight major chromosomal rearrangement events that occurred soon after the teleost-specific genome duplication. CONCLUSIONS: The ddRAD-seq approach combined with the Ion Torrent Personal Genome Machine sequencing allowed us to conduct efficient and flexible SNP genotyping. The integration of the genetic map and the assembled sequence provides a valuable resource for fine mapping and positional cloning of quantitative trait loci associated with economically important traits and for investigating comparative genomics of the Japanese eel.


Subject(s)
Anguilla/genetics , Biological Evolution , Genome , Animals , Chromosome Mapping , Female , Gene Duplication , Gene Library , Genetic Linkage , Genotype , High-Throughput Nucleotide Sequencing , Japan , Male , Microsatellite Repeats , Polymorphism, Single Nucleotide , Sequence Analysis, DNA
6.
Surg Today ; 44(12): 2300-4, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24473668

ABSTRACT

PURPOSE: The aim of this retrospective study was to identify the risk factors associated with the severity characteristics in the Tokyo guidelines for conversion to open surgery in patients with acute cholecystitis (AC) who underwent laparoscopic cholecystectomy. METHODS: A total of 225 patients were enrolled in the study. The patients were classified into two groups: a conversion group and a no-conversion group. The preoperative characteristics and therapeutic strategy were analyzed as risk factors for conversion to open surgery. The postoperative outcomes were also analyzed. RESULTS: Conversion to open surgery occurred in 29 patients (12.9%), including seven patients (6.7%) with mild AC and 22 patients (18.5%) with moderate AC. A univariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h, an elevated C-reactive protein (CRP) value and the Tokyo guidelines 2013 (TG 13) severity classification. The multivariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h and a CRP value >11.5 mg/dl. CONCLUSIONS: A duration of symptoms longer than 72 h, which is included in the criterion for moderate AC severity in the TG 13, was an independent risk factor for conversion to open surgery. In addition, adoption of a high CRP value as an additional criterion for moderate AC may increase the utility of the TG 13.


Subject(s)
Cholecystectomy, Laparoscopic , Cholecystitis, Acute/surgery , Practice Guidelines as Topic , Severity of Illness Index , Aged , Biliary Tract Surgical Procedures/methods , Biomarkers/blood , C-Reactive Protein/analysis , Cholecystitis, Acute/diagnosis , Female , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Tokyo , Treatment Outcome
7.
Surg Today ; 44(1): 160-5, 2014 Jan.
Article in English | MEDLINE | ID: mdl-22932840

ABSTRACT

This report presents the case of a common hepatic artery (CHA) pseudoaneurysm secondary to postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD), which was successfully treated using a coronary covered stent. A 70-year-old female underwent subtotal stomach-preserving PD for middle cholangiocarcinoma. POPF was identified on postoperative day (POD) 7, and the patient suddenly lost 500 ml of blood via the abdominal drain on POD 19. Urgent celiac arteriography revealed a CHA pseudoaneurysm. A coronary covered stent was placed to prevent rupture of the pseudoaneurysm and to maintain hepatic arterial flow, instead of performing transarterial embolization. No vascular adverse events were encountered during or after the procedure. Computed tomography and angiography showed a patent stent graft and good hepatic arterial flow 9 months after placement of the stent. Endovascular stent-graft placement not only treated the pseudoaneurysm, but also preserved the arterial blood flow. This report describes the placement of a covered stent graft for delayed hemorrhage after PD.


Subject(s)
Aneurysm, False/surgery , Endovascular Procedures/methods , Hepatic Artery , Pancreaticoduodenectomy , Stents , Aged , Aneurysm, False/etiology , Aneurysm, Ruptured/prevention & control , Bile Duct Neoplasms/surgery , Cholangiocarcinoma/surgery , Female , Hemorrhage/etiology , Hemorrhage/therapy , Hepatic Artery/physiology , Humans , Liver Circulation , Pancreatic Fistula/etiology , Postoperative Complications/etiology , Treatment Outcome
8.
Rev Sci Instrum ; 84(6): 064501, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23822359

ABSTRACT

We present a novel setup for measuring the effective gas-water permeability of methane-hydrate-bearing sediments. We developed a core holder with multiple pressure taps for measuring the pressure gradient of the gas and water phases. The gas-water flooding process was simultaneously detected using an X-ray computed tomography scanner. We successfully measured the effective gas-water permeability of an artificial sandy core with methane hydrate during the gas-water flooding test.

9.
J Phys Chem A ; 117(20): 4108-14, 2013 May 23.
Article in English | MEDLINE | ID: mdl-23607335

ABSTRACT

The solid-state (13)C NMR spectra of various guest hydrocarbons (methane, ethane, propane, adamantane) in clathrate hydrates were measured to elucidate the local structural environments around hydrocarbon molecules isolated in guest-host frameworks of clathrate hydrates. The results show that, depending on the cage environment, the trends in the (13)C chemical shift and line width change as a function of temperature. Shielding around the carbons of the guest normal alkanes in looser cage environments tends to decrease with increasing temperature, whereas shielding in tighter cage environments tends to increase continuously with increasing temperature. Furthermore, the (13)C NMR line widths suggest, because of the reorientation of the guest alkanes, that the local structures in structure II are more averaged than those in structure I. The differences between structures I and II tend to be very large in the lower temperature range examined in this study. The (13)C NMR spectra of adamantane guest molecules in structure H hydrate show that the local structures around adamantane guests trapped in structure H hydrate cages are averaged at the same level as in the α phase of solid adamantane.


Subject(s)
Furans/chemistry , Hydrocarbons/chemistry , Carbon Isotopes , Furans/chemical synthesis , Magnetic Resonance Spectroscopy/standards , Reference Standards , Water/chemistry
10.
J Hepatobiliary Pancreat Sci ; 20(3): 348-55, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22869101

ABSTRACT

BACKGROUND: This study examined the feasibility of early laparoscopic cholecystectomy (ELC) for acute cholecystitis (AC) according to the Tokyo guidelines severity grade, and analyzed the changes in the therapeutic strategy for AC after the Tokyo guidelines were published. METHODS: A total of 225 patients were enrolled in this study. The therapeutic period was divided into two periods: before and after the publication of the Tokyo guidelines (prior to and including 2007, and from 2008, respectively). RESULTS: Comparing the surgical strategy between ELC and delayed laparoscopic cholecystectomy (DLC), significant differences were found in the length of preoperative hospital stay and total hospital stay for cases of mild AC compared with moderate AC. With conversion to open surgery, postoperative complications including postoperative bile leak were not significantly different. Since ELC was performed significantly more often after publication of the guidelines, preoperative, postoperative, and total hospital stays were significantly shorter in the later period. CONCLUSION: ELC is a safe and effective therapeutic strategy for both mild and moderate AC. The Tokyo guidelines resulted in a significant increase in the performance of ELC and significantly reduced preoperative and total hospital stays without increasing intra- and postoperative complications.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Cholecystitis, Acute/surgery , Practice Guidelines as Topic , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/epidemiology , Severity of Illness Index , Statistics, Nonparametric , Time Factors , Treatment Outcome
11.
Fish Physiol Biochem ; 39(4): 895-905, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23179912

ABSTRACT

The pancreatic digestive enzymes, trypsin, chymotrypsin, lipase and amylase were partially characterized, and changes in their activities were examined during the initial ontogeny of Japanese eel Anguilla japonica larvae from 5 to 34 days post-hatching (dph). The pH optima of the eel larval enzymes were narrower than those other fish species; trypsin activity was highest at pH 9, chymotrypsin and amylase activities were highest at pH 7 and 8, and lipase activity was highest at pH 8 and 9. In an analysis of thermal profiles, the larval pancreatic enzymes had a high optimal temperature and high thermal stability, which are typical of fish from the tropics. At 12 and 13 dph, lipase activity and gene expression levels of trypsin (-a and -b), lipase and amylase decreased markedly, suggesting a marked change in larval metabolism at that time. These data could be useful in the development of artificial larval diets in Japanese eel.


Subject(s)
Anguilla/metabolism , Digestion , Pancreas/enzymology , Amylases/metabolism , Anguilla/growth & development , Animals , Chymotrypsin/metabolism , Fish Proteins/metabolism , Hydrogen-Ion Concentration , Larva/enzymology , Lipase/metabolism , Temperature , Trypsin/metabolism
12.
J Hepatobiliary Pancreat Sci ; 19(4): 476-86, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22033864

ABSTRACT

BACKGROUND: We performed bacteriological analysis of bile in acute cholecystitis (AC) patients graded in severity according to the Tokyo guidelines. METHODS: We enrolled 163 AC patients in whom bacteriological analysis of bile was performed. RESULTS: Significant differences in age (60 vs. 67 years), body temperature (BT) (37.2 vs. 37.6°C), white blood cell count (13,033 vs. 15,177/mm(3)), and serum C-reactive protein (CRP) (8.9 vs. 16.9 mg/dL) were found between the Mild and Moderate severity groups. The prevalence of bactibilia differed significantly between Mild and Moderate patients (45.3 vs. 67.0%, P = 0.0107); however, there were no significant differences in the bacterial strains, prevalence of antimicrobial resistance, or polymicrobial isolation frequency between the 2 groups. Our local antibiogram revealed that several microorganisms showed higher resistance rates; these were also isolated even in Mild cases. Advanced age, high BT, high serum CRP, and presence of marked local infection were identified as being significantly associated with high risk of bactibilia. Receiver operating characteristic curve analysis indicated the optimal cutoff value of age to be 65 years, of BT to be 37.5°C, and of serum CRP to be 13.4 mg/dL. CONCLUSION: Adequate broad-spectrum antimicrobial therapy should be administered perioperatively even for Mild patients classified according to the current Tokyo guidelines. These results suggest that more precise severity grades may need to be established, including age and CRP as additional parameters.


Subject(s)
Bile/microbiology , Cholecystitis, Acute/microbiology , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Female , Humans , Male , Middle Aged , ROC Curve , Sensitivity and Specificity , Severity of Illness Index
13.
Surg Today ; 41(12): 1670-3, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21969204

ABSTRACT

We herein report a case of combined hepatic resection with inferior vena cava (IVC) and diaphragm resection, and reconstruction using an equine pericardial patch. A 54-year-old woman showed hepatic cancer recurrence on radiological imaging, with invasion to the caudate lobe of the liver, IVC, diaphragm, and adrenal gland. We resected 10 × 5 cm of the diaphragm. After dissecting the hepatic parenchyma, the caudate lobe was connected only to the IVC. Clamping of the IVC was performed between the IVC below the confluence of the hepatic vein and the suprarenal IVC. A 6 × 3-cm segment of the IVC was then resected. The IVC and diaphragm were reconstructed using an equine pericardial patch, as both defects were too large to repair without a patch. The equine pericardium represents a suitable graft material for repairing both the IVC and diaphragm. Further investigation is needed to determine the durability and anti-infection properties of equine pericardial grafts.


Subject(s)
Blood Vessel Prosthesis , Diaphragm/surgery , Liver/surgery , Pericardium/transplantation , Vena Cava, Inferior/surgery , Animals , Diaphragm/pathology , Female , Horses , Humans , Liver/pathology , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Vena Cava, Inferior/pathology
14.
Phys Chem Chem Phys ; 13(41): 18481-4, 2011 Nov 07.
Article in English | MEDLINE | ID: mdl-21938303

ABSTRACT

Direct measurements of the dissociation behaviors of pure methane and ethane hydrates trapped in sintered tetrahydrofuran hydrate through a temperature ramping method showed that the tetrahydrofuran hydrate controls dissociation of the gas hydrates under thermodynamic instability at temperatures above the melting point of ice.

15.
J Phys Chem A ; 115(32): 8889-94, 2011 Aug 18.
Article in English | MEDLINE | ID: mdl-21744826

ABSTRACT

The dissociation of C(2)H(6) hydrate particles by slow depressurization at temperatures slightly below the ice melting point was studied using optical microscopy and Raman spectroscopy. Visual observations and Raman measurements revealed that ethane hydrates can be present as a metastable state at pressures lower than the dissociation pressures of the three components: ice, hydrate, and free gas. However, they decompose into liquid water and gas phases once the system pressure drops to the equilibrium boundary for supercooled water, hydrate, and free gas. Structural analyses of obtained Raman spectra indicate that structures of the metastable hydrates and liquid water from the hydrate decay are fundamentally identical to those of the stable hydrates and supercooled water without experience of the hydration. These results imply a considerably high energy barrier for the direct hydrate-to-ice transition. Water solidification, probably induced by dynamic nucleation, was also observed during melting.

16.
Surg Today ; 41(6): 872-6, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21626340

ABSTRACT

A 58-year-old female patient presented with the sudden onset of left upper quadrant pain. The physical examination revealed the presence of shock status. Abdominal computed tomography revealed splenomegaly with a huge mass inside the spleen, and massive fluid collection in the abdominal cavity. After splenic artery embolization, laparotomy was performed. The operative findings revealed intra-abdominal hemorrhage and rupture of the lower pole of the spleen. Furthermore, a palpable solid mass was observed at the splenic hilum, and distal pancreatectomy with splenectomy was performed. The macroscopic findings revealed a pancreatic tail tumor at the splenic hilum directly invading the splenic parenchyma. Microscopic examinations showed the tumor to consist of squamous cell carcinoma. Furthermore, old and new thrombi were observed inside small splenic arteries. These findings were considered to represent invasion of pancreatic adenosquamous carcinoma to the spleen, and rupture of the spleen was attributed to splenic ischemia resulting from cancer invasion and splenic vein obstruction.


Subject(s)
Carcinoma, Adenosquamous/surgery , Pancreatic Neoplasms/surgery , Splenic Neoplasms/surgery , Splenic Rupture/surgery , Carcinoma, Adenosquamous/complications , Carcinoma, Adenosquamous/secondary , Embolization, Therapeutic , Female , Hemoperitoneum/etiology , Humans , Middle Aged , Pancreatectomy , Pancreatic Neoplasms/pathology , Shock, Hemorrhagic/etiology , Splenectomy , Splenic Artery , Splenic Neoplasms/complications , Splenic Neoplasms/secondary , Splenic Rupture/etiology , Splenic Rupture/therapy
17.
Surg Today ; 41(5): 630-6, 2011 May.
Article in English | MEDLINE | ID: mdl-21533933

ABSTRACT

PURPOSE: A total of 7345 cases of digestive organ surgery were investigated over the course of 20 years. METHODS: Owing to the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections, we classified our countermeasures into periods A (September 1987 to February 1990), B (March 1990 to February 1997), C (March 1997 to February 1999), D (March 1999 to October 2004), and E (November 2004 to August 2007), and compared the number of infections during these periods. In period B, cefazolin and cefotiam were administered as prophylaxis. The treatment continued for 4 days, including the day of surgery. The patients undergoing endotracheal intubation or tracheotomy were managed with nonscreening pre-emptive isolation and cohorting (NSPEI&C), regardless of whether MRSA was present. However, NSPEI&C was halted in period C, but it was thereafter implemented again, and prophylactic antibiotics were administered only on the day of surgery during period D. In period E, prophylactic antibiotics were administered for 3 days. RESULTS: In period A, MRSA was contracted in 4.1% (34/833) of patients. In period B, the MRSA isolation rate decreased to 0.3% (8/2722). In period C, the MRSA isolation rate increased to 3.4% (23/681). In period D, the MRSA isolation rate fell to 2.2% (40/1807). In period E, MRSA isolation cases significantly decreased to 0.4% (5/1302; P < 0.002 vs period D). CONCLUSION: The comprehensive management, selection of prophylactic antibiotics, and NSPEI&C were all considered to be effective.


Subject(s)
Cross Infection/prevention & control , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections/prevention & control , Surgical Wound Infection/prevention & control , Antibiotic Prophylaxis , Female , Humans , Male , Patient Isolation , Staphylococcal Infections/etiology , Staphylococcal Infections/microbiology , Surgical Wound Infection/microbiology
20.
J Antimicrob Chemother ; 66(5): 1096-9, 2011 May.
Article in English | MEDLINE | ID: mdl-21393125

ABSTRACT

OBJECTIVES: Clostridium difficile produces toxins and is an aetiological organism of pseudomembranous colitis. Immunoglobulin is one of the treatment strategies against fulminant C. difficile infections, but the clinical evidence is still limited. We examined the efficacy of intravenous immunoglobulin (IVIg) in C. difficile toxin (CDT)-mediated lethality and cellular injury in mice. METHODS: Mice were intraperitoneally injected with 0.2 mL of filter-sterilized C. difficile culture supernatant (CDT preparation). The IVIg preparation was intravenously administered at several timepoints. We also examined alteration of intestinal permeability and an apoptosis marker in the gut. In in vitro experiments, HEp-2 cells were incubated with a CDT preparation in the presence or absence of the IVIg preparation, after which cell viability and lactate dehydrogenase release were examined. RESULTS: All control mice died by day 2 after injection of the CDT preparation. The maximum effects of IVIg (100% survival) were observed when the mice were treated with IVIg at the same time as injection of the CDT preparation. The IVIg effects were closely associated with improvement of intestinal vascular permeability and mucosal damage in the gut. In addition, reduction of an apoptosis marker (histone-associated DNA fragments) was demonstrated in the mice treated with IVIg. Interestingly, a smaller increase in histone-associated DNA fragments was observed in FasL-deficient mice treated with the CDT preparation compared with wild-type. CONCLUSIONS: These data demonstrated that IVIg may be protective against CDT-mediated lethality, when administered at the appropriate time. The present data also suggest an increase in intestinal permeability, probably through exaggeration of Fas/FasL-mediated apoptosis, as a key mechanism of C. difficile-mediated diseases.


Subject(s)
Antitoxins/administration & dosage , Clostridioides difficile/pathogenicity , Clostridium Infections/therapy , Immunoglobulins, Intravenous/administration & dosage , Animals , Cell Line/drug effects , Cell Survival , Clostridium Infections/mortality , Disease Models, Animal , Hepatocytes/drug effects , Humans , Immunotherapy/methods , L-Lactate Dehydrogenase/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Survival Analysis , Treatment Outcome
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