The Correlation Study between Plasma Aß Proteins and Cerebrospinal Fluid Alzheimer's Disease Biomarkers.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-ß proteins (Aß). In this study we explored the correlation of plasma Aß40 and Aß42 concentrations with Aß42, total tau (tTau) and phosphorylated tau 181 (pTau181) levels in cerebrospinal fluid (CSF) in AD and control subjects to further understand the characteristics of plasma Aß proteins levels. METHODS: The consecutive subjects (44 AD and 47 controls) in this study were recruited. The plasma levels of Aß40 and Aß42 were measured using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kits. And the corresponding CSFs were analyzed in terms of Aß42, tTau and pTau181 concentrations using INNOTEST ELISA kits. Further, the albumin levels were measured both in serum and CSF and albumin ratio was obtained to check the integrity of blood-brain barrier. RESULTS: CSF Aß42 concentrations were significantly decreased while tTau and pTau181 levels were significantly increased in AD subjects. The plasma levels of Aß42 were significantly lower (p=0.007), while the Aß40/Aß42 ratio was significantly higher (p<0.001) in AD patients than in controls. The overall plasma Aß42 levels showed a positive correlation with those of CSF Aß42 (p=0.001), but not with the others in CSF. In subgroup analysis, the CSF Aß42 demonstrated positive correlation with not only plasma Aß42 but also Aß40 levels in controls. However, no significant relationship was noted between plasma and CSF Aß proteins in AD group. CONCLUSIONS: The plasma Aß42 and Aß40 concentrations were shown to have a close relationship with CSF Aß42 levels in controls, but not in AD subjects. Our results suggest that the correlation between plasma Aß40 and CSF Aß42 levels is perturbed in AD.

Capsaicin induces apoptosis of cisplatin-resistant stomach cancer cells by causing degradation of cisplatin-inducible Aurora-A protein.

Various chemotherapeutic agents such as cisplatin have been used to treat gastric cancer. However, a substantial number of patients acquire resistance to this treatment, and this is followed by rapid relapse of the disease. We investigated the anticancer effect of capsaicin, the active ingredient in red pepper, in the cisplatin-resistant Korean human gastric cancer cell line SNU-668. We found that treatment of SNU-668 cells with capsaicin in combination with cisplatin induced higher apoptotic cell death than that of treatment with either capsaicin or cisplatin alone. Furthermore, we discovered that Aurora-A protein increased in response to cisplatin and was degraded upon combined treatment with capsaicin with cisplatin, suggesting that the Aurora-A-mediated signaling pathway is responsible for the resistance to cisplatin in cisplatin-resistant gastric cancer cell lines. Combined treatment with capsaicin and cisplatin induced G1/S arrest, whereas cisplatin alone caused accumulation in G2/M. Combined treatment with capsaicin and cisplatin inhibited IκB phosphorylation in a dose-dependent manner, suggesting that Aurora-A directly or indirectly regulates NF-κB translocation. We propose that combined administration of cisplatin and capsaicin may provide a strategy for overcoming cisplatin resistance.

Fetal death of dogs after the ingestion of a soil conditioner.

Castor beans (Ricinus communis) contain ricin, which is one of the most toxic substances of plant origin. Ricin toxicosis has been reported in different countries with usually ingestion of castor beans or plants in both animals and humans. However, ricin toxicosis by ingestion of some products containing castor oil cake has rarely been reported. This paper describes outbreaks of dog death by ricin toxicosis after accidental ingestion of the same soil conditioner. Fifteen dogs showed toxic symptoms such as severe vomiting, abdominal pain and hemorrhagic diarrhea, and then thirteen dogs died in a few days. The soil conditioner dogs ingested consisted of 10% castor oil cake containing ricin. On the basis of clinical signs, laboratory and pathologic findings, a diagnosis of ricin toxicosis was established in the present case. In comparison with previous cases by ingestion of castor beans, the dogs' morbidity was very high in the present case. The ingestion of castor oil cake may be more dangerous to life than the castor beans. It is because mortality by ingestion of castor beans depends on the degree of mastication of the beans, whereas ricin in oil cake is easily absorbed from the stomach and the intestines. As ricin is a heat-labile toxin, products containing ricin or oil cake should be properly treated with heat and have written caution sentences about toxicosis, and be kept out of reach of domestic animals and children.

Fibroma with osseous metaplasia of external auditory canal in a dog.

The present report describes a case of fibroma with osseous metaplasia of the external auditory canal in a 7-year-old male Pomeranian dog. Upon otoscopic examination, the right external auditory canal was almost completely obstructed by a well-circumscribed mass adjacent to the eardrum. The mass was surgically excised. Grossly, it was well demarcated, firm when cut, pink, and measured 0.3 cm x 0.2 cm x 0.7 cm. The cut surface of the mass exhibited a central portion of homogeneously white osseous components surrounded by brown to pink soft tissue. Microscopically, the resected external auditory canal mass mainly consisted of fibroblastic spindle cells showing differentiation to metaplastic osteoblast-like cells. Metaplastic osteoblasts and osteoclasts lining the osteoid bony trabeculae were also observed. Bony trabeculae and spicules were separated by abundant collagen and neoplastic fibroblastic cells. Fibromatous components, irregular formation of woven bone spicules, and the presence of osteoblasts lining bony trabeculae led to a diagnosis of fibroma with osseous metaplasia.

The optimal size and placement of transdermal electrodes are critical for the efficacy of a transcutaneous pacemaker in dogs.

Transcutaneous cardiac pacing (TCP) can be used in dogs with a high risk for bradyarrhythmias prior to anesthesia, either in an emergency room or intensive care unit setting. Furthermore, TCP can also be used on patients diagnosed with bradyarrhythmias that require temporary pacing at the induction of anesthesia for the implantation of a permanent pacemaker. Despite the importance of TCP in emergency medicine, no studies have evaluated the optimal size and placement of the transdermal electrodes crucial for the efficacy of TCP in dogs. This study evaluated four different sizes of electrodes (10.5, 20, 30 and 40 cm2), and four different anatomical sites (anterior-posterior, left-right, apex-base, modified left-right) in order to optimize the efficacy of TCP in dogs. Electrodes with a surface area of 20 cm2 and a modified left-right placement minimized the pacing current and involuntary skeletal muscular contraction (muscular twitching) and so achieved the most optimal effect of TCP in dogs.

Urethral stenting in a cat with refractory obstructive feline lower urinary tract disease.

A 10-year-old male Korean domestic short-haired cat was presented with refractory lower urinary tract obstruction. The cat was treated by urethral stent placement using a self-expanding nitinol intraluminal stent (Zilver 535 biliary stents, COOK, U.S.A.) subsequent with balloon expansion. Although the cat showed 2 days of transient hematuria after the stent placement, no further obstruction was occurred after the stent placement. Follow-up studies performed at monthly intervals have found no re-stenosis or particular complications, to date.

Potent neutralization of vacuolating cytotoxin (VacA) of Helicobacter pylori by immunoglobulins against the soluble recombinant VacA.

BACKGROUND: The recombinant vacuolating cytotoxin (rVacA) of Helicobacter pylori that retains native conformational epitopes was evaluated as a vaccine antigen for anti-H. pylori treatment. METHODS: s1m1 vacA gene fraction encoding the mature VacA protein was expressed as a soluble protein in E. coli at low temperature. The efficacy of anti-rVacA antibody against VacA or H. pylori was assessed in vitro using AGS cells and in vivo using a murine model. RESULTS: The rabbit antisera against rVacA completely neutralized the vacuolating activity and partially inhibited the cell death induced by VacA in AGS cells. Oral immunization of C57BL/6 mice with rVacA plus CpG-oligodeoxynucleotide (ODN) as an ajuvant stimulated specific anti-VacA antibody and mucosal immune responses which correlated with decreased systemic immune responses and gastric urease activities (p>0.05). CONCLUSION: The rVacA antigen possessing conformational epitopes may have potential as a vaccine component and may be useful in serological and histopathological analysis.

Evaluation of changes in cardiac biomarker concentrations and enzyme activities in serum after short- and long-duration transcutaneous cardiac pacing in dogs.

OBJECTIVE: To evaluate serum cardiac biomarker concentrations and selected enzyme activities in dogs with experimentally induced bradyarrhythmias after short- (1-hour) and long- (3-hour) duration transcutaneous cardiac pacing (TCP). ANIMALS: 10 healthy Beagles. PROCEDURES: In each dog, anesthesia was induced with propofol (5 mg/kg, IV) and maintained via inhalation of isoflurane in oxygen. To induce bradyarrhythmia, diltiazem was administered IV (20 to 50 mg/dog). Transcutaneous cardiac pacing was performed for 1 hour (5 dogs) or 3 hours (5 dogs) by use of an automated external cardiac pulse generator and a transdermal electrode. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase were evaluated the day before (baseline) and at intervals until 7 days after TCP. RESULTS: Increases (from baseline) in serum cardiac biomarker concentrations and enzyme activities were detected in the long-duration TCP group; changes in the short-duration TCP group were more minor and largely not significant. Although severity of myocardial and skeletal muscular injuries was apparently greater with greater duration of TCP, the injuries were not persistent; most variables were within reference range within 3 days after TCP. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that application of TCP for > 1 hour in dogs may cause myocardial and skeletal muscular injuries. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase should be more carefully monitored after TCP of > 1 hour's duration to evaluate potential myocardial damages.

Ebstein's anomaly with an atrial septal defect in a jindo dog.

A 7-month-old, female jindo dog was presented with severe ascites, cyanosis, and exercise intolerance. Diagnostic imaging studies revealed Ebstein's anomaly with an atrial septal defect. The dog was managed medically with inotropics, diuretics, and vasodilators.

Phosphorylation of hepatitis B virus Cp at Ser87 facilitates core assembly.

Protein-protein interactions can be regulated by protein modifications such as phosphorylation. Some of the phosphorylation sites (Ser155, Ser162 and Ser170) of HBV (hepatitis B virus) Cp have been discovered and these sites are implicated in the regulation of viral genome encapsidation, capsid localization and nucleocapsid maturation. In the present report, the dimeric form of HBV Cp was phosphorylated by PKA (protein kinase A), but not by protein kinase C in vitro, and the phosphorylation of dimeric Cp facilitated HBV core assembly. Matrix-assisted laser-desorption ionization-time-of-flight analysis revealed that the HBV Cp was phosphorylated at Ser87 by PKA. This was further confirmed using a mutant HBV Cp with S87G mutation. The S87G mutation inhibited the phosphorylation and, as a result, the in vitro HBV core assembly was not facilitated by PKA. In addition, when either pCMV/FLAG-Core(WT) or pCMV/FLAG-Core(S87G) was transfected into HepG2 cells, few mutant Cps (S87G) assembled into capsids compared with the wild-type (WT) Cps, although the same level of total Cps was expressed in both cases. In conclusion, PKA facilitates HBV core assembly through phosphorylation of the HBV Cp at Ser87.

Renal and ureteral fusion in a calf with atresia ani.

A 10-day old male calf exhibited multiple congenital anomalies of the urinary and gastrointestinal tracts, including renal fusion (horseshoe kidney), ureteral fusion, rectovesicular fistula, and atresia ani. In horseshoe kidney, the organs were fused together at the caudal poles. The left kidney and cranial half of right kidney were shrunken, while the remaining lobules were hypertrophic. Ureters were fused cranially and bifurcated caudally. The terminal rectum was narrowed and connected with the bladder. The anus was imperforate. The cause of these anomalies could not be determined.