Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.

Evaluation of fecal microbiomes associated with obesity in captive cynomolgus monkeys (Macaca fascicularis)

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.

Reference values of hematological and biochemical parameters in young-adult cynomolgus monkey (Macaca fascicularis) and rhesus monkey (Macaca mulatta) anesthetized with ketamine hydrochloride / 한국실험동물학회지

Nonhuman primate models are valuable in biomedical research. However, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. In the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. A total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference intervals of 20 hematological and 16 biochemical parameters. The effects of sex were also investigated. Reference intervals for hematological and biochemical parameters were separately established by species (cynomolgus and rhesus) and sex (male and female). No sex-related differences were determined in erythrocyte-related parameters for cynomolgus and rhesus monkey housed in indoor laboratory conditions. Alkaline phosphatase and gamma glutamyltransferase were significantly lower in females than males in both cynomolgus and rhesus monkeys aged 48–96 months. The reference values for hematological and biochemical parameters established herein might provide valuable information for researchers using cynomolgus and rhesus monkeys in experimental conditions for biomedical studies.

Mutations of DPC4/Smad4 Gene in Gallbladder Carcinoma

PURPOSE: The DPC4/Smad4 gene is known to perform a key role in the TGF-beta group protein signaling pathway, which regulates cell proliferation, differentiation and death. DPC4/ Smad4 gene mutation has been studied in cancers of the breast, ovary, esophagus, colo-rectum, bile duct, as well as the pancreas. The mutation rates depend on the kind of carcinoma sites, and range from 10% to around 50%, but no study has been performed on gallbladder carcinomas. This study was performed to search for mutation of the DPC4/Smad4 gene in the gallbladder carcinomas. METHODS: Eighteen surgically resected gallbladder cancers were screened for mutation of the exons; 8, 9, 10 and 11 of the DPC4/Smad4 gene using dideoxyfingerprinting (ddF), and single strand conformational polymorphism (SSCP). The results were confirmed using automatic DNA sequencing, and the expressions examined by immunohistochemical staining with the monoclonal anti-DPC4/Smad4 protein antibody, B8. RESULTS: DdF revealed 3 mutations in two of the exons, which were confirmed by direct sequencing. In one case, a single-base substitution mutation existed in exon 11 with codon change (missense mutation), whereas in two cases such mutations were detected in exon 9 without codon change (silent mutation). Immunohistochemical staining showed negative to weakly positive expression for all three mutated cases, but had high false-positive rates (7/11). CONCLUSION: DPC4/Smad4 gene mutation exists in a certain proportion of gallbladder carcinomas, but the mutation rate seems to be low compared to organogenetically related pancreas or bile duct carcinomas. This suggests somewhat different mechanisms may operate on the carcinogenesis of these organs.

A Case of a Bleeding Duodenal Diverticulum by a Dieulafoy-like Lesion / 대한소화기내시경학회지

Duodenal diverticula are first reported by Chomel in 1710. Duodenal diverticula are relatively common in adults with a prevalence of 23% in ERCP. The most duodenal diverticulum is asymptomatic. Complications such as obstruction, cholangitis, biliary stones, ulceration, perforation and hemorrhage can occur in approximately 10%. However, relatively few cases of bleeding from a duodenal diverticulum have been reported. The cause of bleeding from a duodenal diverticulum is uncertain and various suspected etiologies were suggested, such as ectopic gastric mucosa, stasis-induced ulceration, erosion into major vessels, aortoenteric fistulas, intradiverticular polyp, aspirin-induced erosion. We report a case of a bleeding duodenal diverticulum by a Dieulafoy-like lesion and suggest this lesion as one of possible causes of bleeding in duodenal diverticulum.

Two Cases of Multiple Carcinoid Tumors of the Rectum / 대한소화기내시경학회지

Carcinoid tumors of the rectum are relatively uncommon and comprise only about one percent of all rectal neoplasms. Typically, rectal carcinoids present as small, solitary submucosal nodules and have benign course. But, multicentricity is rare. The frequency of an associated second malignancy is about 13%. The explanation of the high frequency of other neoplasms associated with carcinoid tumors is still unclear. We have experienced two cases of multiple carcinoid tumors of the rectum, one was coexisted with adenocarcinoma of the sigmoid colon. They presented with mass on the right inguinal area and hematochezia. Carcnoids was found incidentally. Because the tumors measured 15 mm or less in diameter, did not infiltrate beyond the submucosal layer and had no histological atypia, carcinoids was treated by endoscopic polypectomy and mucosal resection. Thereafter, one underwent surgery for adenocarcinoma of the sigmoid colon. Herein we present our experience with reviewed literatures.

A Case of the Duodenal Tuberculosis Presenting as Hematemesis / 대한소화기내시경학회지

Despite the modern advance in effective chemotherapy, gastrointestinal tuberculosis is considered to be relatively frequent in developing countries. The ileocecal region is the most common site of intestinal tuberculosis and duodenal involvement is rare. The isolated duodenal tuberculosis are reported 9 cases in Korea. The symptoms and signs of gastrointestinal tuberculosis are nonspecific and vague. In the absence of pulmonary tuberculosis, the diagnosis may be difficult. Pain and vomiting are common symptoms of duodenal tuberculosis. Patients may present with upper gastrointestinal bleeding. Therefore, tuberculosis should be considered in the differential diagnosis of gastrointestinal bleeding. We herein report a case of duodenal tuberculosis presenting as hematemesis and necessitating hospitalization. After anti-tuberculosis therapy, we have confirmed the healing of the lesion by the follow-up endoscopy, and review the current literature.