Early activation of myocardial matrix metalloproteinases and degradation of cardiac troponin I after experimental subarachnoid hemorrhage.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in acute myocardial dysfunction by degrading several intracellular contractile proteins, including cardiac troponin I (cTnI). Here, we examined the temporal profiles of MMPs and cTnI in plasma and myocardial tissue in the acute stage of subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: SAH was induced by the endovascular suture method in rats. Intracranial pressure and left ventricular (LV) function were recorded. Plasma cTnI and MMPs were measured at 0, 5, 15, 30, 60, 120, and 180 minutes after SAH. Myocardial cTnI and MMP activities were quantified at 30, 60 and 180 min after SAH from homogenized hearts. RESULTS: SAH-induced rats showed a marked decline in -LV dP/dt(max) (index of LV diastolic function). Plasma samples revealed a noticeable increase in cTnI and pro-MMP-9 activities over the course of 180 minutes. In myocardial tissue, there was a marked increase in pro-MMP-9, pro-MMP-2 activities and expression of activated MMP-2. Western blot analysis revealed a striking decrease in cTnI content and increase in cTnI degradation in myocardium. Simultaneous cTnI depletion and MMP-2 expression in myocardium was detected by immunohistochemistry as early as 30 minutes after SAH. MMPs correlated with -LV dP/dt(max) (% of baseline) both in plasma and in myocardial tissue. Furthermore, activated MMP-2 activity correlated positively with cTnI degradation in myocardium. CONCLUSIONS: Early activation of MMPs was observed in myocardium and plasma following SAH. Activated MMP-2 may regulate proteolytic cTnI and contribute to myocardium stunning injury in SAH rats.

Bronchiolitis obliterans organizing pneumonia in Swine associated with porcine circovirus type 2 infection.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a chronic respiratory disease. Although the pathogenesis of BOOP is still incompletely understood, BOOP is responsive to steroids and has a good prognosis. In our five pigs with chronic postweaning multisystemic wasting syndrome (PMWS), typical BOOP lesions were revealed. All five porcine lungs showed typical intraluminal plugs, and porcine circovirus type 2 (PCV2) was identified. They also exhibited similar pathologic findings such as proliferation of type II pneumocytes and myofibroblasts (MFBs), extracellular collagen matrix (ECM) deposition, and fragmentation of elastic fibers. MFBs migration correlative molecules, for instance, gelatinase A, B and osteopontin, appeared strongly in the progressing marginal area of polypoid intraluminal plugs of fibrotic lesion. These molecules colocalized with the active MFBs. Both gelatinase activity and intercellular level of active MFBs were significantly increased (P < .05). Porcine chronic bronchopneumonia leads to BOOP and it is associated with PCV2 persistent infection. Swine BOOP demonstrates similar cellular constituents with human BOOP. Perhaps their molecular mechanisms of pathogenesis operate in a similar way. Thus we infer that the swine BOOP can be considered as a potential animal model for human BOOP associated with natural viral infection. Moreover, it is more convenient to obtain samples.

The Efficacy and Safety of Tube Feeding in Advanced Dementia Patients: A Systemic Review and Meta-Analysis Study.

OBJECTIVES: The current study aimed to conduct a systematic review and meta-analysis to explore the efficacy and safety of tube feeding in patients with advanced dementia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: PubMed, Medline, Embase, and Cochrane Library were searched from inception until March 7, 2020, to obtain relevant studies. INTERVENTION: Feeding with nasogastric tube or percutaneous endoscopic gastrostomy (PEG). MEASURES: We evaluated the associations of tube feeding and the risk of mortality, period of survival days, tube-related complications, and nutritional status. Data from original studies were synthesized by using a random-effects model. Each selected article was assessed for bias using the Newcastle-Ottawa Scale. A narrative synthesis and pooled analyses are reported. RESULTS: Twelve trials were eligible, involving 1805 patients with tube feeding (mean age: 82.8 years; 71.3% female) and 3861 without tube feeding (mean age: 82.7; 68.7% female). For mortality rate, patients with advanced dementia with tube feeding are associated with significantly higher mortality rate [k = 8; odds ratio (OR) 1.79; 95% confidence interval (CI) 1.04-3.07; P = .03]. Initially, no association was found for the risk of pneumonia and pressure sore between groups. However, sensitivity analysis showed patients with advanced dementia with PEG tube feeding have significantly higher risk of pneumonia (OR 3.56; 95% CI 2.32-5.44; P < .001) and pressure sore (OR 2.25; 95% CI 1.92-2.63; P < .001). Finally, no association was found for the survival period and nutritional status between groups. CONCLUSIONS AND IMPLICATIONS: This meta-analysis indicates that tube feeding is associated with increased mortality rate and possible tube-related complications, but not improves with prolonging survival days and nutritional status. Shared decision-making routinely before insertion of a tube between caregivers and physicians is recommended.

Isolation of Trypanosoma (Megatrypanum) theileri from dairy cattle in Taiwan.

Although Trypanosoma (Megatrypanum) theileri, a blood parasite of bovid species, is spread widely throughout the world, it has never been reported in Taiwan. When an anti-coagulated blood sample from febrile dairy cattle was directly smeared, no parasite was observed. However, a highly distinctive morphological feature of trypanosome appeared in baby hamster kidney (BHK) cell culture inoculated with non-thrown blood buffy coat. The different stages and typical ultrastructures of trypanosome were observed in our isolate. The isolate was subsequently identified as T. theileri by species-specific PCR assay (Tth625), 18S rDNA sequencing alignment and internal transcribed spacer of ribosomal genes (ITS) as a marker for molecular phylogenetic analysis. The first T. theileri isolate in Taiwan (TWTth1) could be periodically passaged in BHK cell culture for more than one year and retained good re-cryopreservation viability. The BHK culture method would be excellent for diagnostic isolation and maintenance long-term development of this parasite.

Effects of Shugan-Huayu powder, a traditional Chinese medicine, on hepatic fibrosis in rat model.

Shugan-Huayu powder (SHP) has been administered to outpatients with chronic liver disease without clear anti-fibrosis mechanism. To investigate the anti-fibrotic effects of SHP on liver fibrosis in a rat model and in hepatic stellate cells (HSCs) in vitro, rats were gavaged with CCl4 at 1.0 g/kg body weight twice a week for 8 weeks to induce liver fibrosis and the rats were randomly assigned to one of the three groups: -CCl4 alone, low-dose SHP and high-dose SHP. SHP was given by gavages 5 times a week for 8 weeks. Serum, livers and HSCs were assayed for serology, pathology, western blot, zymography and quantitative RT-PCR. Hepatic function improved as decreased serum aspartate aminotransferase and alanine aminotransferase, and collagen deposition and active HSCs were significantly reduced in CCl4-induced liver by SHP treatment. The expression of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta1 (TGF-beta1) mRNA in fibrotic liver showed significant downregulation after SHP treatment. In vitro, inhibition of alpha-smooth muscle actin (alpha-SMA) expression and MMP-2 secretion of active HSCs were also noticed by SHP treatment. SHP has an antifibrotic effect on CCl4-induced liver fibrosis in rats. Anti-fibrotic mechanisms were probably inhibiting activation of HSCs and decreased expression of MMP-2 and TGF-beta1.

Clinical and molecular genetic features of cerebrotendinous xanthomatosis in Taiwan: Report of a novel CYP27A1 mutation and literature review.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder associated with mutations in the CYP27A1 gene, and the genetic features of CTX in Taiwanese have not been examined before. OBJECTIVES: We report a new CTX family with a novel mutation in the CYP27A1 gene and analyze the clinical and molecular genetic features of CTX in Taiwan. METHODS: The clinical and molecular genetic features of the two siblings from the new CTX family and the other 7 reported Taiwanese CTX patients were included for analysis. The clinical features of the enrolled CTX patients were recorded using the indicators that make up the suspicion index (SI). RESULTS: The age at CTX diagnosis of the two siblings in the new CTX family were in late 30s, and predominantly psychiatric features. Both siblings had compound heterozygous splicing mutations in the CYP27A1 gene, including one mutation in exon 2 (c.435G>T, cryptic splice site) and one mutation in intron 7 (c.1264A>G, canonical splice site). None of the CTX patients in Taiwan were diagnosed during childhood or adolescence, and the most common clinical features of the 9 Taiwanese CTX patients were tendinous xanthomas, followed by ataxia and/or spastic paraparesis, dentate nuclei signal alternation at magnetic resonance imaging, intellectual disability and/or psychiatric disturbance, and polyneuropathy. Mutations in the CYP27A1 gene in the Taiwanese population were most commonly observed in exon 2, followed by exon 8 and intron 7. Except for one CTX patient who had an SI score of 100, the SI scores ranged from 300 to 400 before the study of the CYP27A1 gene and diagnosis. CONCLUSIONS: We reported two Taiwanese CTX siblings who had compound heterozygous mutations in CYP27A1. Exons 2 and 8 and intron 7 are the hotspots for Taiwanese CTX mutations. The diagnosis of CTX in Taiwan is usually delayed and is probably under-recognized based on statistical estimations. Early identification and genetic diagnosis may be helpful to CTX patients because early treatment can reduce the accumulation of cholestanol and slow disease progression.

Antipsychotic-Induced Pisa Syndrome: A 2-Year Follow-up Study.

OBJECTIVES: Pisa syndrome is characterized by lateral trunk flexion. It is an uncommon adverse drug reaction in patients on antipsychotic medication. Although Pisa syndrome has been reported in patients on antipsychotic treatment, previous studies have not discussed the prognosis of patients with Pisa syndrome. We studied psychiatric patients with Pisa syndrome following antipsychotic treatment for a 2-year period. METHODS: From January 2012 to December 2014, 13 inpatients with Pisa syndrome following antipsychotic treatment were identified at our institution, from a prospectively collected database. These patients were studied for a 2-year period. RESULTS: The prevalence rate of Pisa syndrome during neuroleptic treatment was 0.45% in men and 0.37% in women, with a collective prevalence rate of 0.42%. The mean age of patients with Pisa syndrome was 47 years. Eight (61.5%) of the cases had a position with a tilt toward the right side. In 5 (38.5%) of the cases, a tilt toward the left side was observed. The average Cobb angle of the trunk was 17.3 (SD, 4.0) degrees. On presentation with Pisa syndrome within 3 months of medication modification, the pattern of trunk dystonia had a significantly shorter duration (P = .024) compared with that seen in the tardive-onset group. CONCLUSIONS: Pisa syndrome is an uncommon adverse event that can also be chronic or recurrent, especially in those with tardive onset. We should be aware of the risks in patients with the following predisposing factors: old age, chronic psychosis, long-term antipsychotic use, advanced drug-induced parkinsonism, and combined pharmacologic treatment.

DNA sequence analysis of glycoprotein G gene of bovine ephemeral fever virus and development of a double oil emulsion vaccine against bovine ephemeral fever.

The surface glycoprotein G is considered as the major neutralizing and protective antigen of bovine ephemeral fever virus (BEFV). Comparison of the deduced amino acid sequence of G protein of BEFV isolates during the period 1984-2004 outbreaks in Taiwan showed amino acid substitutions in the neutralizing epitopes. All the isolates differ markedly in the neutralizing epitope at the same amino acid positions compared to the currently available killed vaccine strain (Tn73). Tn88128 strain isolated in 1999 showed the maximum variability of 12 amino acids, 5 amino acid in the neutralization epitope and 7 apart from, respectively. Combinations of both Tn88128 (1999) and commercially available vaccine strain (Tn73) were developed and its safety was evaluated in mice, guinea pigs, calves, and pregnant cows. None of the animals showed any adverse effect or clinical signs. Calves were immunized with commercial vaccine (Tn73) and, combined vaccine (Tn73 and Tn88128), respectively, with adjuvants such as Al-gel and water-in-oil-in-water (w/o/w) oil and PBS alone and challenged with Tn88128 strains. Except PBS administered animals, all the vaccinated animals showed protective immune response. However, animals immunized with combined vaccine plus w/o/w adjuvant elicited stronger neutralization antibodies and long lasting immunity compared to other vaccines.

Development of a reliable assay protocol for identification of diseases (RAPID)-bioactive amplification with probing (BAP) for detection of bovine ephemeral fever virus.

A rapid, sensitive, and specific assay, RAPID-BAP assay, was developed to detect and quantify the G protein-encoding gene of bovine ephemeral fever virus (BEFV). This new technique uses a nested PCR and magnetic bead-based DNA probing assay. The optimal conditions for the assay were examined. By applying a nested PCR, a minimum of 1 copy/mul of the BEFV plasmid DNA could be detected by the assay. The optimal hybridization conditions at 50 degrees C in 5x SSC and 0.5% SDS with a 20-min incubation allowed clear discrimination between negative and positive controls. The assay was also highly specific as all negative controls failed to show any positive detection. The diagnostic sensitivity of the RAPID-BAP assay, real-time RT-PCR, and conventional RT-PCR in the detection of 34 clinical blood samples suspected to have BEFV infections were 72.73, 36.36, and 18.18%, respectively. The results indicated that the RAPID-BAP assay developed in this study was more sensitive than the conventional RT-PCR and real-time RT-PCR assays for the detection of BEFV. The novel RAPID-BAP assay is an excellent diagnostic tool with high sensitivity, specificity, and fast turnaround time.

High-Dose Risperidone Induced Latent Syndrome of Inappropriate Antidiuretic Hormone Secretion With Seizure Presentation.

We report a case of a patient with schizophrenia treated with high-dose risperidone, who developed syndrome of inappropriate antidiuretic hormone secretion (SIADH) with the only early symptom of tonic-clonic seizures. A 40-year-old woman with schizophrenia was treated with risperidone 2 mg/d. After the dosage was titrated to 6 mg/d, she experienced generalized seizure attacks. Laboratory screening revealed that the serum sodium level was 106 mmol/L, the urine sodium concentration was 41.2 mmol/L, and the urine osmolality was 371 mOsm/kg H2O. A diagnosis of SIADH was made, and risperidone was stopped. After infusion of hypertonic saline, the serum sodium returned to normal levels, and seizures did not recur. In this patient, SIADH advanced in a latent manner because the first and only symptom of SIADH was seizure attack. High-dose risperidone treatment is the most probable cause, and the mechanisms may be related to risperidone's high affinity for the 5-hydroxytryptamine 2A and dopamine 2 receptors. Patients with schizophrenia can display atypical features of medical illnesses. Routine physical and laboratory examinations may prevent silent disease progression.

Effects of mycophenolate mofetil on cutaneous lupus erythematosus in (NZB × NZW) F1 mice.

BACKGROUND: Few studies have evaluated the effects and precise molecular mechanism of mycophenolate mofetil (MMF) in the treatment of human cutaneous lupus erythematosus (CLE). Our findings shed light on the therapeutic effects of MMF in a UVB-induced NZB × NZW (NZBW) F1 CLE mouse model. METHODS: Continuous MMF treatment (60 mg/kg/day) was administered up to Day 50 from the beginning of UVB induction (Day 0; 20 weeks old), as the pathologic features of CLE are present after 50 days. The therapeutic effects of MMF treatment in NZBW lupus mice were examined by comparing histopathological changes, lupus band test (deposition of immune complexes at the dermal-epidermal junction) and colocalization of autoantibodies with a dermal autoantigen Dsg3, and by evaluating the associations of local matrix metalloprotease activities. RESULTS: MMF improved survival in the NZBW lupus mice from 35.7% to 81.8%. The proteinuria, blood urea nitrogen, and interleukin 6 levels were significantly reduced after MMF treatment. The dermal lymphocytic infiltration, deposition of immune complexes at the dermal-epidermal junction, colocalized autoantibodies with Dsg3, and epidermal matrix metalloprotease activity were also attenuated in MMF-treated NZBW F1 mice. CONCLUSION: The results confirmed that MMF could substantially attenuate skin damage due to CLE in the NZBW F1 mouse model.

Evidence of intracellular stages in Trypanosoma (Megatrypanum) theileri in non-phagocytic mammalian cells.

Trypanosoma (subgenus Megatrypanum) theileri was first identified over one hundred years ago, and is a widespread parasite in cattle. Its life cycle within the mammalian host has rarely been reported. Whether there is an intracellular stage in tissues is unknown and such a stage has not been demonstrated experimentally. Intriguingly, using Giemsa staining with light microscopy and transmission electron microscopy examination, we found that the parasite was able not only to attach to cells but also to invade several phagocytic and non-phagocytic mammalian cells. Based on these findings, we conducted further investigations using a special antibody in immunofluorescence confocal images. Moreover, we examined a series of possible events of cell invasion in T. theileri. The results revealed that GM1, a marker of membrane rafts, was implicated in the mechanism of entry by this parasite. After incubation with tissue culture trypomastigotes, the gelatinolytic activity was significantly increased and accumulated at the attachment sites. Using ultrastructural localization detection by CytoTracker live imaging and confocal immunofluorescence microscopy, we found that lysosome fusion and the autophagy pathway were engaged in invaginating processes. T. theileri amastigotes also invaded cells and were enclosed by the lysosomes. Furthermore, tissue-cultured trypomastigotes were found to be capable of triggering intracellular free Ca(2+) transients and TGF-ß-signaling. Our findings that intracellular amastigote stages exist in mammalian cells infected with T. theileri and that the invasion processes involved various host cell components and cell signalings were extremely surprising and warrant further investigation.