Venous thromboembolisms and rheology in ovarian cancer patients after postoperative adjuvant paclitaxel and carboplatin therapy.

In ovarian cancer patients, chemotherapy can be an independent risk factor for the development of thromboembolic complications, such as venous thromboembolism (VTE). The factors and their values that lead to the development of VTE are remaining unknown in patients undergoing chemotherapy with paclitaxel and carboplatin. This study investigated serial rheological parameters (D-dimer, red blood cell count, hematocrit, and plasma viscosity) for VTE that developed following chemotherapy for ovarian cancer. Forty-eight ovarian cancer patients undergoing chemotherapy were enrolled in this study. A significant difference in the mean values of plasma viscosity and hematocrit was observed between the VTE group (n = 5) and the non-VTE group (n = 43) (P < 0.10). Univariate and multiple regression analyses by stepwise selection identified plasma viscosity as the independent variable associated with VTE development. The VTE incidence was the same as in previous reports. The results support the contention that plasma viscosity could be an index for development of VTE in ovarian cancer after chemotherapy.

Angiopoietin-like protein 2 promotes chondrogenic differentiation during bone growth as a cartilage matrix factor.

OBJECTIVE: Chondrocyte differentiation is crucial for long bone growth. Many cartilage extracellular matrix (ECM) proteins reportedly contribute to chondrocyte differentiation, indicating that mechanisms underlying chondrocyte differentiation are likely more complex than previously appreciated. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor normally abundantly produced in mesenchymal lineage cells such as adipocytes and fibroblasts, but its loss contributes to the pathogenesis of lifestyle- or aging-related diseases. However, the function of ANGPTL2 in chondrocytes, which are also differentiated from mesenchymal stem cells, remains unclear. Here, we investigate whether ANGPTL2 is expressed in or functions in chondrocytes. METHODS: First, we evaluated Angptl2 expression during chondrocyte differentiation using chondrogenic ATDC5 cells and wild-type epiphyseal cartilage of newborn mice. We next assessed ANGPTL2 function in chondrogenic differentiation and associated signaling using Angptl2 knockdown ATDC5 cells and Angptl2 knockout mice. RESULTS: ANGPTL2 is expressed in chondrocytes, particularly those located in resting and proliferative zones, and accumulates in ECM surrounding chondrocytes. Interestingly, long bone growth was retarded in Angptl2 knockout mice from neonatal to adult stages via attenuation of chondrocyte differentiation. Both in vivo and in vitro experiments show that changes in ANGPTL2 expression can also alter p38 mitogen-activated protein kinase (MAPK) activity mediated by integrin α5ß1. CONCLUSION: ANGPTL2 contributes to chondrocyte differentiation and subsequent endochondral ossification through α5ß1 integrin and p38 MAPK signaling during bone growth. Our findings provide insight into molecular mechanisms governing communication between chondrocytes and surrounding ECM components in bone growth activities.

Effect of serotonin transporter genotype on self-reported efficacy and activity changes of brain prefrontal area in response to placebo.

Patients benefit from drug therapy not only through pharmacological mechanisms, but also through non-pharmacological action (placebo effect), which may be mediated in part by the prefrontal area of the brain. We consider that the difference between responders and non-responders to placebo might be related to polymorphisms in the serotonin transporter-linked polymorphic region (5-HTTLPR). To study this idea, we performed a randomized double-blind clinical trial using caffeine and lactose (placebo). Activity in the prefrontal area of the brain was measured in terms of blood flow by means of near-infrared spectroscopy (NIRS) as an objective indicator. Self-reported feelings of drowsiness on established scales were used as subjective indicators. Twenty-one subjects in block A took caffeine on the first day and placebo on the third day, and 21 in block B took placebo on the first day and placebo on the third day. After placebo administration, improvement of sleepiness was significantly enhanced, a similar extent to that after caffeine medication. Among the 42 subjects, 22 showed S/S type polymorphism in the serotonin transporter (52.4 %), 17 showed S/L type (40.5 %) and 3 showed L/L type (7.10 %). Statistical analysis of the results indicate that subjects with L/L genotype showed a significantly greater placebo response in terms of both self-reported feeling of drowsiness and blood flow in the prefrontal area of the brain associated with working memory (46 area). Our results indicate that the L/L genotype of 5-HTTLPR, which is rare in Japanese (3.2 %) but common in Americans (32.2 %), may be associated with a greater placebo effect.

Mosaic KCNJ2 mutation in Andersen-Tawil syndrome: targeted deep sequencing is useful for the detection of mosaicism.

Andersen-Tawil syndrome (ATS) is an inherited disease characterized by ventricular arrhythmias, periodic paralysis, and dysmorphic features. It results from a heterozygous mutation of KCNJ2, but little is known about mosaicism in ATS. We performed genetic analysis of KCNJ2 in 32 ATS probands and their family members and identified KCNJ2 mutations in 25 probands, 20 families who underwent extensive genetic testing. These tests revealed that seven probands carried de novo mutations while 13 carried inherited mutations from their parents. We then specifically assessed a single proband and the respective family. The proband was a 9 year old girl who fulfilled the ATS triad and carried an insertion mutation (p.75_76insThr). We determined that the proband's mother carried a somatic mosaicism and that the proband's younger brother also carried the ATS phenotype with the same insertion mutation. The mother, who exhibited mosaicism, was asymptomatic, although she exhibited Q(T)U prolongation. Mutant allele frequency was 11% as per TA cloning and 17.3% as per targeted deep sequencing. Our observations suggest that targeted deep sequencing is useful for the detection of mosaicism and that the detection of mosaic mutations in parents of apparently sporadic ATS patients can help in the process of genetic counseling.

Therapeutic window of lamotrigine for mood disorders: a naturalistic retrospective study.

INTRODUCTION: Lamotrigine is widely used for mood disorders including bipolar disorder and major depression, but its therapeutic levels have yet to be determined. This study was conducted to investigate the hypothesis that lamotrigine may have a therapeutic window for mood disorders. METHODS: 25 patients with mood disorders received lamotrigine for more than one year during which time plasma lamotrigine levels were measured at least once. Their mental state was retrospectively and regularly but blindly assessed using the Clinical Global Impression-Severity (CGI-S) scale. In order to investigate our hypothesis, we depicted the relationship between the last lamotrigine levels and the last CGI scores in 25 patients. If any, the potential therapeutic window was further investigated. RESULTS: The relationship between the last lamotrigine levels and the last CGI scores in the 25 patients indicated the presence of a therapeutic window of lamotrigine from 5 to 11 µg/mL. The repeated measures of ANOVA reached a significant tendency of the effects of lamotrigine levels within 5-11 µg/mL on better CGI-S scores, and the CGI-S scores at the last observation of the 15 patients whose lamotrigine levels were within 5-11 µg/mL were significantly better than those of 10 patients whose lamotrigine levels were not within 5-11 µg/mL. CONCLUSION: These findings suggest that lamotrigine may have a therapeutic window for patients with mood disorder from 5 to 11 µg/mL.

Intraoperative hypertensive crisis in a dog with functional paraganglioma of the gall bladder.

A 15-year-old spayed female mongrel presented with anorexia and an abdominal mass. The mass originated from the gall bladder and was surgically resected along with divisionectomy of the central hepatic division. Paroxysmal hypertension and tachycardia were noted during manipulation of the mass. Following resection, arterial blood pressure decreased significantly. Histopathological analysis confirmed a diagnosis of neuroendocrine neoplasm. Immunohistochemical staining for synaptophysin and chromogranin A yielded diffuse and strong positive results, while gastrin was positive in only 10% of the cells. The preoperative elevated concentrations of catecholamine in the urinalysis showed a marked decrease after surgery. Based on these findings, the tumour was diagnosed as a functional paraganglioma of the gall bladder. The patient has undergone regular thoracic radiographs and ultrasound examinations and, until 431 days after surgery, has shown no signs of metastases or recurrences. Based on our literature search, we report the first case of functional paraganglioma of the gall bladder in a dog.

Collective excitation of an electric dipole on a molecular dimer in an organic dimer-Mott insulator.

The terahertz response in 10-100 cm(-1) was investigated in an organic dimer-Mott (DM) insulator κ-(ET)(2)Cu(2)(CN)(3) that exhibits a relaxorlike dielectric anomaly. An ~30 cm(-1) band in the optical conductivity was attributable to collective excitation of the fluctuating intradimer electric dipoles that are formed by an electron correlation. We succeeded in observing photoinduced enhancement of this ~30 cm(-1) band, reflecting the growth of the electric dipole cluster in the DM phase. Such optical responses in κ-(ET)(2)Cu(2)(CN)(3) reflect an instability near the boundary between the DM-ferroelectric charge ordered phases.

Dipeptidyl peptidase-4 inhibitors and angioedema: a class effect?

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to be generally well tolerated. However, angioedema has been reported as one of the rare adverse events of these drugs. CASE REPORT: We report a case in which angioedema induced by vildagliptin disappeared after changing to another DPP-4 inhibitor, alogliptin. DISCUSSION: Our case suggests that there is a difference in the risk of angioedema among DPP-4 inhibitors. To clarify this possibility, further investigation on the risk of angioedema among DPP-4 inhibitors is warranted.

Effect of pilocarpine on substance P and calcitonin gene-related peptide releases correlate with salivary secretion in human saliva and plasma.

WHAT IS KNOWN AND OBJECTIVE: Pilocarpine, a muscarinic receptor agonist, has been used for the treatment of dry mouth. Salivary glands are supplied with nerve fibres that contain neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP), which are important modulators of salivation. It is known that measurement of salivary and plasma levels of neuropeptides is useful for assessing the dose-pharmacological effect relationship of drugs. The relationship between the action of pilocarpine and neuropeptides in humans has not been studied. Moreover, studies evaluate the usefulness of drug salivary levels in the pharmacological evaluation of drugs are scarce. The aim of this study was to examine the effects of pilocarpine on the levels of substance P-, CGRP- and VIP-like immunoreactive substances (IS) in saliva and plasma taken in healthy humans. METHODS: Five healthy male subjects participated in this study. Pilocarpine tablet (10 mg) or placebo tablet was orally administered with 100 mL of water. Each subject was administered placebo and drug with an interval of 4 weeks in between. Saliva was sampled before and at 20, 40, 60, 90, 120, 180 and 240 min after administration of the test substances. Venous blood samples (10 mL) were also taken from a forearm vein at each time interval. The samples were then enzyme immunoassayed using a highly sensitive system for substance P-, CGRP- and VIP-IS. The amount of saliva was measured by the Saxon test. RESULTS: A single oral administration of pilocarpine increased the release of salivary substance P-IS (the area under the concentration-time curve: AUC(0→240 min)) compared with the placebo. Pilocarpine also significantly increased the release of salivary CGRP-IS (AUC(0→240 min)). Pilocarpine significantly increased the release of plasma CGRP-IS. The salivary volume correlated with the salivary level of substance P and CGRP-IS (r = 0·84, P < 0·05 and r = 0·59, P < 0·05, respectively). AUC(0→240 min) for substance P-IS in saliva correlated with that for plasma (r = 0·78, P < 0·05). WHAT IS NEW AND CONCLUSION: Pilocarpine increases the release of salivary substance P and CGRP-IS. This suggests that one mechanism by which pilocarpine improves dry mouth is by local stimulation of neuropeptidergic nerves. Moreover, saliva levels of substance P showed good correlation with the plasma levels. The substance P levels in saliva and plasma may be good indicators of the effects of drugs used in dry mouth/xerostomic patients.

The role of serum adiponectin levels in women with polycystic ovarian syndrome.

PURPOSE OF INVESTIGATION: The aim of this study was to measure serum adiponectin concentrations in women with polycystic ovarian syndrome (PCOS) and to assess possible correlations between adiponectin and the hormonal or metabolic parameters of this syndrome. MATERIALS AND METHODS: Serum adiponectin levels were evaluated in 20 women with PCOS and 22 women without PCOS whose age and body mass index (BMI) matched the patients. The levels of fasting blood glucose, fasting insulin, gonadotropin, and sex steroid hormones were evaluated in both groups. The homeostasis model assessment (HOMA) score was also calculated. The serum adiponectin levels were assayed by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: Serum adiponectin levels were significantly lower in obese women than in normal-weight women, and they were also significantly lower in PCOS patients with HOMA scores greater than 1.7 compared with those with HOMA scores lower than 1.7. When the subjects were divided in two groups based on serum adiponectin levels (> 40 microg/ml, < 40 microg/ml), 65% of patients with PCOS were included in the lower adiponectin group (p < 0.05). In addition, gonadotropin levels were increased, dependent on the adiponectin levels in women with PCOS. CONCLUSION: Adiponectin is regarded as a possible link between adiposity and insulin resistance (IR). From this data, the secretions of gonadotropin are implicated in the levels of adiponectin in women with PCOS. It is suggested that adiponectin may play an important role in the pathogenesis of PCOS.

Acceleration of diabetes development in CXC chemokine receptor 3 (CXCR3)-deficient NOD mice.

AIMS/HYPOTHESIS: The aim of this study was to understand the role of CXC chemokine receptor 3 (CXCR3), a T-helper 1(Th1) type chemokine receptor, in the pathogenesis of type 1 diabetes. METHODS: We observed the incidence of diabetes in Cxcr3 homozygous knockout mice. We compared the expression pattern of various cytokines and chemokines and the frequency of FOXP3(+) cells in the pancreas and pancreatic lymph nodes from Cxcr3 ( -/- ) NOD mice and wild-type NOD mice. In addition, we observed the migration ability of CXCR3(+)CD4(+) cells to pancreatic islets upon adoptive transfer. Finally, we examined whether Cxcr3 (+) regulatory T cells (Tregs) actually suppressed the onset of diabetes in vivo. RESULTS: Cxcr3 ( -/- ) NOD mice developed spontaneous diabetes earlier than did wild-type NOD mice. In Cxcr3 ( -/- ) NOD mice, Tregs were more frequent in pancreatic lymph nodes and less frequent in pancreatic islets than in wild-type NOD mice. While transferred CXCR3(-)CD4(+) cells from wild-type NOD mice did not infiltrate pancreatic islets of NOD-severe combined immunodeficiency (SCID) mice, CXCR3(+)CD4(+) cells from the same mice migrated into the recipient islets and contained Forkhead box P3 (FOXP3) upon adoptive transfer. Moreover, CD4(+)CD25(+) cells from wild-type NOD mice suppressed and delayed the onset of diabetes compared with those from Cxcr3 ( -/- ) NOD mice in a cyclophosphamide-induced diabetes model system. CONCLUSIONS/INTERPRETATION: The mechanism of accelerated diabetes onset in Cxcr3 ( -/- ) NOD mice was considered to be due to the lack of hybrid Tregs (CXCR3(+)FOXP3(+)CD4(+) cells), which could effectively migrate into and regulate Th1 inflammation in local lesions under Cxcr3 knockout conditions.

Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer.

BACKGROUND: The expression of L-type amino-acid transporter 1 (LAT1) is tumour-specific and has been shown to have essential roles in cell growth and survival. However, little is known regarding the clinical significance of LAT1 expression in pancreatic cancer. This study was conducted to determine the prognostic significance of LAT1 expression. METHODS: A total of 97 consecutive patients with surgically resected pathological stage I-IV pancreatic ductal adenocarcinoma were retrospectively reviewed. Tumour sections were stained by immunohistochemistry for LAT1, CD98, Ki-67 and vascular endothelial growth factor (VEGF), and microvessel density was determined by CD34 and p53. RESULTS: L-type amino-acid transporter 1 and CD98 were highly expressed in 52.6% (51/97) and 56.7% (55/97) of cases, respectively (P=0.568). The expression of LAT1 within pancreatic cancer cells was significantly associated with disease stage, tumour size, Ki-67, VEGF, CD34, p53 and CD98. L-type amino-acid transporter 1 expression was confirmed to be a significant prognostic factor for predicting poor outcome by multivariate analysis. CONCLUSION: L-type amino-acid transporter 1 expression is a promising pathological marker for the prediction of outcome in patients with pancreatic cancer.

Role of mineralocorticoid receptor/Rho/Rho-kinase pathway in obesity-related renal injury.

OBJECTIVE: We examined whether aldosterone/Rho/Rho-kinase pathway contributed to obesity-associated nephropathy. SUBJECTS: C57BL/6J mice were fed a high fat or low fat diet, and mice on a high fat diet were treated with a mineralocorticoid receptor antagonist, eplerenone. RESULTS: The mice on a high fat diet not only developed obesity, but also manifested renal histological changes, including glomerular hypercellularity and increased mesangial matrix, which paralleled the increase in albuminuria. Furthermore, enhanced Rho-kinase activity was noted in kidneys from high fat diet-fed mice, as well as increased expressions of inflammatory chemokines. All of these changes were attenuated by eplerenone. In high fat diet-fed mice, mineralocorticoid receptor protein levels in the nuclear fraction and SGK1, an effector of aldosterone, were upregulated in kidneys, although serum aldosterone levels were unaltered. Furthermore, aldosterone and 3ß-hydroxysteroid dehydrogenase in renal tissues were upregulated in high fat diet-fed mice. Finally, in cultured mesangial cells, stimulation with aldosterone enhanced Rho-kinase activity, and pre-incubation with eplerenone prevented the aldosterone-induced activation of Rho kinase. CONCLUSION: Excess fat intake causes obesity and renal injury in C57BL/6J mice, and these changes are mediated by an enhanced mineralocorticoid receptor/Rho/Rho-kinase pathway and inflammatory process. Mineralocorticoid receptor activation in the kidney tissue and the subsequent Rho-kinase stimulation are likely to participate in the development of obesity-associated nephropathy without elevation in serum aldosterone levels.

Triglyceride-rich lipoproteins in chronic kidney disease patients undergoing maintenance haemodialysis treatment.

OBJECTIVE: Plasma triglyceride (TG) levels were reported to be high in chronic kidney disease (CKD) patients undergoing haemodialysis (HD) treatment. One of the atherogenic causes of hypertriglyceridemia is the increase in TG-rich lipoprotein remnants, which are equivalent to remnant-like particle cholesterol (RLP-C). Here, we compared the plasma levels of TG, a representative indicator of TG-rich lipoproteins and RLP-C, as well as the TG/RLP-C ratio between CKD patients undergoing HD and controls, in an effort to elucidate the atherogenicity of TG-rich lipoproteins in CKD patients on HD. MATERIALS AND METHODS: Plasma lipid and apo(lipo)protein levels and the TG/RLP-C ratio were compared between 49 CKD patients undergoing HD and 627 controls. Blood sampling for lipid and apoprotein analysis was performed in a 12-h fasting state. Controls were divided into four subgroups according to TG level (from highest to lowest). RLP-C and apo(lipo)proteins were measured using the immunoprecipitation method and turbidimetric immunoassay, respectively. In addition, a comparison between HD patients and age-, gender-, and plasma TG level-matched controls was performed. RESULTS: Plasma TG levels were 107 ± 70 (mean ± SD) mg/dl in HD patients and 115 ± 72 mg/dl in controls. Plasma RLP-C levels were 6.7 ± 4.5 mg/dl in HD patients and 4.6 ± 3.5 mg/dl in the controls (p < 0.0001). RLP-C levels decreased in descending order from the highest to the lowest TG group in controls. RLP-C levels were higher in HD patients than in controls with plasma TG levels of < 150 mg/dl (p < 0.0001). TG/RLP-C ratios were 19.0 ± 12.0 in HD patients and 25.9 ± 9.5 in controls (p < 0.0001). This ratio was significantly lower in HD patients than in all four TG subgroups. The comparison between HD patients and age-, gender-, plasma TG-matched controls revealed identical results. CONCLUSION: Plasma RLP-C levels were high, and the TG/RLP-C ratio was low in CKD patients undergoing HD treatment. These findings indicate that total plasma TG-rich lipoprotein levels were not increased, but the distribution of plasma TG-rich lipoproteins were skewed towards remnant fractions in CKD patients undergoing HD treatment; these plasma TG-rich lipoproteins appear to be more atherogenic than those in controls.

Complex regulation of the TIR1/AFB family of auxin receptors.

Auxin regulates most aspects of plant growth and development. The hormone is perceived by the TIR1/AFB family of F-box proteins acting in concert with the Aux/IAA transcriptional repressors. Arabidopsis plants that lack members of the TIR1/AFB family are auxin resistant and display a variety of growth defects. However, little is known about the functional differences between individual members of the family. Phylogenetic studies reveal that the TIR1/AFB proteins are conserved across land plant lineages and fall into four clades. Three of these subgroups emerged before separation of angiosperms and gymnosperms whereas the last emerged before the monocot-eudicot split. This evolutionary history suggests that the members of each clade have distinct functions. To explore this possibility in Arabidopsis, we have analyzed a range of mutant genotypes, generated promoter swap transgenic lines, and performed in vitro binding assays between individual TIR1/AFB and Aux/IAA proteins. Our results indicate that the TIR1/AFB proteins have distinct biochemical activities and that TIR1 and AFB2 are the dominant auxin receptors in the seedling root. Further, we demonstrate that TIR1, AFB2, and AFB3, but not AFB1 exhibit significant posttranscriptional regulation. The microRNA miR393 is expressed in a pattern complementary to that of the auxin receptors and appears to regulate TIR1/AFB expression. However our data suggest that this regulation is complex. Our results suggest that differences between members of the auxin receptor family may contribute to the complexity of auxin response.

Pediatric perfusion in Japan: 2010 practice survey.

We report here Japan's first pediatric perfusion survey. It covers practices from January 2007 through December 2009. Of the 70 congenital heart centers contacted, 53 (76%) completed the survey. They reported performing 3,379 pediatric cardiopulmonary bypass (CPB) procedures in 2009, 3,408 in 2008, and 3,358 in 2007.Twenty-eight percent of all centers used CPB circuits with a priming volume between 151-200 ml. All centers used pre-bypass ultrafiltration and only 6% used retrograde autologous priming. A biomaterial-coated circuit was used by 78% of the centers, a roller pump as the arterial pump by 91%, vacuum-assisted venous drainage by 39%, dilutional ultrafiltration by 48%, and modified ultrafiltration at the end of the procedure by 30%. A regional oxygen saturation monitor was used by 69% of the centers and high flow (150-200 ml/kg/min) management with alpha-stat blood gas control was standard during moderate to normothermic CPBs. Crystalloid cardioplegia solution was used as myocardial protection by 56% of the centers, electronic recording of monitoring data by 51%. The centers performed 98 pediatric extracorporeal membrane oxygenation procedures in 2007, 109 in 2008, and 119 in 2009; 58% of the centers used a centrifugal pump. This survey provides a description of the current practice in Japan. Future surveys will identify trends and rate of change in practice.

Transient ligation of umbilical vessels elevates placental tissue oxygen index (TOI) values measured by near-infrared spectroscopy (NIRS) in clawn miniature pig animal model.

We recently found a significant elevation in placental tissue oxygen index (TOI) values in cases of fetal growth restriction using near-infrared spectroscopy (NIRS), indicating high oxygenation in the placental tissue. We hypothesized that insufficient fetoumbilical blood flow is causatively associated with high oxygenation levels in placental tissue. We transiently (for 15 sec) ligated the whole umbilicus, umbilical arteries, or veins of pregnant Clawn miniature pigs (102-113 days of gestation) and assessed the changes in TOI values of the placenta and fetus. The ligation significantly increased placental TOI values (p<0.01, respectively), but concomitantly decreased fetal TOI values (p<0.01, respectively), suggesting a decline in oxygen inflow from the maternal to fetal circulation in the placental tissue to be causative of the elevated placental TOI values. These observations suggest the promising clinical use of placental TOI values measured noninvasively by the transabdominal application of NIRS to assess the fetoplacental circulation.

Clinical relationship between histopathological necrotic/partial necrotic findings and disease condition of gallbladder mucoceles in dogs.

Gallbladder mucocele (GM) is a common extrahepatic biliary disease recognized in dogs and is defined as the expansion and extension of the gallbladder by an accumulation of semi-solid bile or bile acid. Histopathological diagnosis of necrotizing cholecystitis and transmural coagulative necrosis of the gallbladder wall shows poor prognosis. Conversely, histopathological diagnosis with partial necrotic findings is often achieved. We hypothesized that histopathological partial necrosis of the gallbladder wall is the primary lesion of necrotic cholecystitis or transmural ischemic necrosis. Therefore, we investigated the relationship between histopathological necrosis/ partial necrosis findings and their clinical conditions. We retrospectively analyzed 55 dogs diagnosed with GM that had undergone cholecystectomy at the Yamaguchi University Animal Medical Center. The group with histopathological necrosis/partial necrosis of the gallbladder wall showed elevated levels of preoperative white blood cells, alanine transaminase, alkaline phosphatase, γ-glutamyltransferase, total bilirubin, and C-reactive protein compared to the non-necrotic group. Partial necrosis of the gallbladder wall may affect the progression of the disease and hematological abnormalities. Additionally, all death cases until 2 weeks were included in the histopathological necrosis/partial necrosis group. In this study, we found that poor prognosis factors were associated with partial necrosis of the gallbladder wall. Furthermore, these cases of partial necrosis showed elevated levels of blood test parameters. These results suggest that necrosis of the gallbladder wall is associated with poor prognosis and poor pathophysiological conditions.