A. castellanii and P. aeruginosa mutually exacerbate damage to corneal cells during coinfection.

IMPORTANCE: At the National Cheng Kung University Hospital, numerous cases of amoebic keratitis had been identified with concurrent bacterial infections. Among these bacterial coinfections, Pseudomonas aeruginosa accounted for 50% of the reported cases. However, the impact of pathogenic bacteria on amoeba-induced corneal damage remains unclear. In our study, we successfully demonstrated that P. aeruginosa accumulated on the Acanthamoeba castellanii surface and caused more severe corneal damage. We also indicated that the exposure of P. aeruginosa to amoeba-soluble antigens enhanced its adhesion ability, promoted biofilm formation, and led to more severe corneal cell damage. These findings significantly contributed to our understanding of the risk associated with P. aeruginosa coinfection in the progression of amoeba keratitis.

Lipid Accumulation in Blastocystis Increases Cell Damage in Co-Cultured Cells.

Blastocystis hominis is an intestinal protozoan that is often neglected, despite causing abdominal pain and diarrhea. Previous research has demonstrated that lipids can be synthesized by B. hominis or can accumulate in growth medium, but their function and mechanisms in the pathogenesis of Blastocystis remain unclear. Our study found that lipid-rich Blastocystis ST7-B can increase inflammation and disrupt Caco-2 cells more than the same parasite without the lipovenoes supplement. Additionally, the cysteine protease of Blastocystis, a virulence factor, is upregulated and has higher activity in lipid-rich Blastocystis. In order to better understand the effects of lipids on Blastocystis pathogenesis, we treated lipid-lowering pravastatin during Blastocystis ST7-B culturing with a lipovenoes supplement, which decreased the lipid levels of the Blastocystis and reduced the Blastocystis-induced inflammation and cell disruption of Caco-2 cells. We also analyzed the fatty acid composition and possible synthesis pathway in Blastocystis ST7-B, finding significantly higher ratios of arachidonic acid, oleic acid, and palmitic acid than in the other lipid components in lipid-rich Blastocystis ST7-B. These results suggest that lipids play a significant role in the pathogenesis of Blastocystis and provide important information on the molecular mechanisms of and potential treatments for Blastocystis infection.

Characterization of tracheotomized patients after spontaneous subarachnoid hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) is a catastrophic event with high disability and fatality rates. Post-SAH survivors may require prolonged intubation with the assistance of mechanical ventilators, and some patients will undergo tracheostomy to facilitate their pulmonary hygiene and airway protection. The aim of this study is to identify the incidence and risk factors of the need for tracheostomy after spontaneous SAH. We used a retrospective approach and enrolled 838 adult patients with a primary diagnosis of spontaneous SAH who survived >7 days after hospitalization. Medical information was retrieved from the administrative database utilizing diagnostic and procedure codes by the International Classification of Diseases, Ninth Revision, Clinical Modification. Patients with first-ever SAH included 329 men and 509 women, and their average age was 56.9 ±â€Š14.4 years, ranging between 18 and 91 years. Fifty-eight of these 838 patients underwent tracheostomy procedures, and the overall incidence was 6.9%. In a multivariate logistic regression model, the independent risk factors of the need for tracheostomy were underlying diabetes mellitus (P = .02), hydrocephalus (P < .01), and pneumonia (P < .01). The mean duration of hospital stay was 26.0 ±â€Š15.3 and 16.8 ±â€Š12.2 days for patients with and without a tracheostomy, respectively (P < .01). In conclusion, a significant percentage of post-SAH survivors underwent tracheostomy during acute hospitalization. Attention to independent risk factors, including preexisting diabetes mellitus, concomitant hydrocephalus, and nosocomial pneumonia, is essential for timely patient selection for tracheostomy.

First molecular identification of Vorticella sp. from freshwater shrimps in Tainan, Taiwan.

Freshwater shrimps are the most common crustaceans kept in an aquarium. This study was a survey seeking parasites infecting cultured freshwater atyid shrimps at aquarium stores in Tainan, Taiwan. We observed that atyid shrimps were infested with Vorticella and Scutariella. Scutariella is a common shrimp parasite; thus, we focused on Vorticella infection in the atyid shrimps. Vorticella aequilata-like pop TW, a freshwater peritrich ciliate, was isolated from the atyid shrimps. The morphological characteristics were investigated using live observations. Specimens from the population showed identical arrangement of the infraciliature and identical ITS1-5.8SITS2 region sequences. The zooids are bell-shaped, 40-58 µm wide and 47-70 µm in long in vivo. The food vacuole is variable in shape and is located in the middle of the cell. ITS1-5.8S-ITS2 sequences of Vorticella aequilata-like pop TW did not match any available sequences in GenBank. Phylogenetically, Vorticella aequilata-like pop TW clusters with the other Vorticella within the family Vorticellidae and nests with Vorticella aequilata in the subclade. Above all, the morphological characteristics and molecular analyses show that the investigated Vorticella is a Vorticella aequilata-like species. The phylogenetic analyses of ciliates based on the ITS1-5.8S-ITS2 sequences reveal that the Vorticella genus consists of Vorticella morphospecies and that taxonomic revision of the genus is needed. Morphometric criteria and molecular analysis were used to describe and identify the Vorticella specie and this study presents the first molecular identification analysis of the Vorticella species in the cultured atyid shrimps in Tainan, Taiwan.

Pathogenic Acanthamoeba castellanii Secretes the Extracellular Aminopeptidase M20/M25/M40 Family Protein to Target Cells for Phagocytosis by Disruption.

Acanthamoeba is free-living protist pathogen capable of causing a blinding keratitis and granulomatous encephalitis. However, the mechanisms of Acanthamoeba pathogenesis are still not clear. Here, our results show that cells co-cultured with pathogenic Acanthamoeba would be spherical and floated, even without contacting the protists. Then, the Acanthamoeba protists would contact and engulf these cells. In order to clarify the contact-independent pathogenesis mechanism in Acanthamoeba, we collected the Acanthamoeba-secreted proteins (Asp) to incubate with cells for identifying the extracellular virulent factors and investigating the cytotoxicity process. The Asps of pathogenic Acanthamoeba express protease activity to reactive Leu amino acid in ECM and induce cell-losing adhesion ability. The M20/M25/M40 superfamily aminopeptidase protein (ACA1_264610), an aminopeptidase be found in Asp, is upregulated after Acanthamoeba and C6 cell co-culturing for 6 h. Pre-treating the Asp with leucine aminopeptidase inhibitor and the specific antibodies of Acanthamoeba M20/M25/M40 superfamily aminopeptidase could reduce the cell damage during Asp and cell co-incubation. These results suggest an important functional role of the Acanthamoeba secreted extracellular aminopeptidases in the Acanthamoeba pathogenesis process. This study provides information regarding clinically pathogenic isolates to target specific molecules and design combined drugs.

Whether CD44 is an applicable marker for glioma stem cells.

Glioblastoma multiforme (GBM) is one of the most malignant and aggressive brain tumors with great amount of hyaluronan (HA) secretion and CD44 overexpression (HA receptor). CD44 has been suggested as a cancer stem cells (CSCs) marker. However, several clinical studies have indicated that CD44low glioma cell exhibit CSCs traits. Additionally, our previous study indicated that more CD44 expression was associated with a better prognosis in GBM patients. To determine whether CD44 is an appropriate marker of glioma stem cells (GSCs), we manipulated CD44 expression using intrinsic (CD44 knockdown, CD44kd) and extrinsic (HA supplement, HA+) methods. Our results show that CD44kd suppressed cell proliferation by retarding cell cycle progression from G0/G1 to S phase. Furthermore, it caused GSCs traits, including lower expression of differentiation marker (glial fibrillary acidic protein, GFAP), a higher level of sphere formation and higher expression of stem cell markers (CD133, nestin and Oct4). The reduction of CD44 expression induced by HA+ was accompanied by an increase in GSCs properties. Interestingly, the presence of HA+ in glioma cells with GSC traits conversely facilitated differentiation. Our data indicated that the CD44 low-expressing cells exhibit more GSCs straits, suggesting that CD44 is not an appropriate marker for GSCs. Furthermore, the preferential expression of CD44 at the invasive rim in rat glioma specimen implies that CD44 may be more important for invasion and migration instead of GSCs marker in glioma.

Demographics and Short-Term Outcomes of Spontaneous Subarachnoid Hemorrhage in Young Adults.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH) is a catastrophic disease with a high mortality. Although it is associated with poor prognosis in older patients, the socioeconomic consequences in younger patients with stroke may be more severe. We aimed to focus on the demographics and short-term outcomes of SAH in a population younger than 50 years. METHODS: We retrospectively enrolled 1689 patients with a primary diagnosis of SAH from 1993 to 2010. We identified intergroup differences in clinical variables between the patients aged 18-49 years (n = 531) and those aged ≥50 years (n = 1158). RESULTS: The patients with SAH included 688 men and 1001 women (an overall male/female ratio of 1:1.45), of whom 31.4% were aged 18-49 years. Men comprised 53.5% of the younger patients and 34.9% of the older patients (P < 0.01). The post-SAH sequela of hemiplegia was more common in the younger patients (P < 0.01), whereas the incidences of in-hospital mortality in the younger and older groups were 25.4% and 32.4%, respectively (P < 0.01). CONCLUSIONS: Adults younger than 50 years account for a significant portion of the population with SAH. There is a male predominance in this age group, probably related to early and substantial risk exposure. Although younger age imparts a higher probability of survival, it is also accompanied by a greater incidence of resultant sequelae. A better understanding of the age-related variability of SAH will assist in guidance for public health and adjustment of clinical management.

Evaluation of cellular retinoic acid binding protein 2 gene expression through the retinoic acid pathway by co-incubation of Blastocystis ST-1 with HT29 cells in vitro.

Blastocystis is a parasitic protist with a worldwide distribution that is commonly found in patients with colon and gastrointestinal pathological symptoms. Blastocystis infection has also commonly been reported in colorectal cancer and HIV/AIDS patients with gastrointestinal symptoms. To understand the pathway networks of gene regulation and the probable mechanisms influencing functions of HT-29 host cells in response to parasite infection, we examined the expression of 163 human oncogenes and kinases in human colon adenocarcinoma HT-29 cells co-incubated with Blastocystis by in-house cDNA microarray and PCR analysis. At least 10 genes were shown to be modified following Blastocystis co-incubation, including those with immunological, tumorigenesis, and antitumorigenesis functions. The expression of genes encoding cellular retinoic acid binding protein 2 (CRABP2) and proliferating cell nuclear antigen (PCNA) was markedly upregulated and downregulated, respectively. Reverse transcriptase-PCR validated the modified transcript expression of CRABP2 and other associated genes such as retinoic acid (RA)-related nuclear-receptor (RARα). Together, our data indicate that CRABP2, RARα, and PCNA expressions are involved in RA signaling regulatory networks that affect the growth, proliferation, and inflammation of HT-29 cells.

Characterization of acute post-craniectomy seizures in traumatically brain-injured patients.

PURPOSE: Decompressive craniectomy (DC) is a life-saving measure for traumatic brain injury (TBI), but acute seizures following this procedure may have a devastating effect. We aim to investigate the clinical characteristics of acute post-craniectomy seizures. METHODS: For this retrospective study, we enrolled 195 patients undergoing DC for TBI. Acute post-craniectomy seizure was defined as seizures occurring within 7 days of DC. RESULTS: The incidence of acute seizure was 10.8% (21/195). 19 of 21 seizures occurred within 3 days following DC. None progressed to status epilepticus, but 16 of 21 patients (76.2%) with acute seizure developed epilepsy. There was no independent risk factor in the multivariate regression model. The mean hospital stay was 44.8 ± 34.6 and 28.8 ± 32.3 days for patients with and without acute seizures, respectively (p=0.035). The neurological outcome at discharge showed no inter-group difference (p=0.917). The in-hospital mortality rate was 28.6% for patients with seizures and 31.0% for patients without seizures (p=0.817). CONCLUSION: Acute seizures occur mostly within the first 3 days following DC. Neurological outcome and mortality rate at discharge does not differ between patients with or without seizures, but the duration of hospital stay is significantly longer for acute seizure patients.

Clinical features and surgical outcomes of sporadic cerebellar hemangioblastomas.

BACKGROUND: Sporadic hemangioblastomas show a strong preference for the cerebellum. We clarify the clinical characteristics and role of surgery in sporadic cerebellar hemangioblastomas. MATERIALS AND METHODS: This 11-year retrospective study enrolled 20 patients (10 men and 10 women; 41.6±9.8 years) with sporadic cerebellar hemangioblastomas. All patients had a solitary tumor and underwent surgical resection of the lesion through a suboccipital midline approach. The basic features, serial radiographic examinations, and operative records were analyzed. RESULTS: The mean follow-up was 39.2±37.4 months (range, 2-134 months). The most common presenting symptoms were headache, vertigo, ataxia, and nausea or vomiting. There were 6 (30.0%) completely solid, 1 (5.0%) combined solid and cystic, and 13 (65.0%) primarily cystic tumors. The average size of the tumor was 40.7±8.7mm in its maximal diameter (range, 25-58mm). Eighteen (90.0%) patients underwent gross total resection and 2 (10.0%) underwent partial resection. After the primary surgery, 16 (80.0%) patients experienced improvement in their symptoms, 4 (20.0%) maintained their pretreatment status, and none showed neurological deterioration following tumor resection. Recurrence and progression were identified in 4 of 20 tumors. Three of the 4 tumors became symptomatic and the patients underwent secondary surgery with total removal of the tumor. CONCLUSION: Sporadic cerebellar hemangioblastomas are usually associated with cysts and are voluminous by the time of diagnosis. Because these tumors result in the mass effect of posterior fossa, surgical removal is preferable and safe, and can be a timely curative strategy to prevent neurological decline.

Experience with Novalis stereotactic radiosurgery for vestibular schwannomas.

BACKGROUND: The Novalis linear accelerator system, a well developed modality, can be used for stereotactic radiosurgery (SRS). The aim of this study was to clarify the efficiency and safety of Novalis SRS in treating vestibular schwannomas. MATERIALS AND METHODS: This 4-year retrospective study enrolled 23 patients with 26 vestibular schwannomas (3 patients suffered from neurofibromatosis Type II). Five patients had undergone tumor resection. All 26 tumors were treated using Novalis SRS, with a prescription dose that varied between 10 and 16Gy (mean, 11.8±1.7Gy). The average follow-up period was 56.5±22.1 months (range, 17-87 months). RESULTS: There were 9 men and 14 women. Their mean age at the time of treatment was 54.0±14.6 years (range, 27-84 years). On average, the original size of the tumor was 19.0±7.2mm in maximal diameter (range, 4.6-39.9mm). At the last follow-up, 20 tumors had regressed (76.9%), and there was no observed change in the size of 3 tumors (11.5%). Three of 26 tumors (11.5%) enlarged more than 2mm in one direction. Thus the ultimate radiological tumor control rate was 88.5% (23/26). In addition, 20 (87.0%) patients retained their pre-irradiation hearing function. Facial and trigeminal nerve function were both preserved in all patients. No death occurred during the follow-up, and no patient was treated with a second SRS or converted to tumor resection. CONCLUSION: Novalis SRS is a reliable treatment option for vestibular schwannomas. With an optimal radiation dose, satisfactory tumor control can be achieved while preserving cranial nerve function.

Is timing of cranioplasty following posttraumatic craniectomy related to neurological outcome?

BACKGROUND: With the use of decompressive craniectomy for traumatic brain injury (TBI) come a corresponding number of cranioplasties. TBI causes dynamic processes to commence or change during the period from injury to recovery; hence, the role of the timing of surgical intervention should be emphasized. AIMS: We attempt to identify the relationship between the timing of cranioplasty and neurological outcomes following posttraumatic craniectomy. METHODS: In this 3-year retrospective study, 105 patients undergoing decompressive craniectomies and subsequent cranioplasties for TBI were enrolled. We documented the patients' demographic information, including Glasgow Coma Scale (GCS) at admission for trauma. The follow-up period was terminated by death or a minimum of 6 months after TBI. Glasgow Outcome Scale (GOS) at the end of follow-up was used as an outcome measure. Unfavorable outcome was defined as a GOS score of 1-3. RESULTS: The 105 patients included 71 male and 34 female subjects. The mean age was 41.94 ± 19.73 years. Neurological assessment showed that admission GCS was 8.50 ± 3.15, on average. The mean time interval between cranioplasty and craniectomy was 78.84 ± 49.04 days (range, 13-245 days). Univariate logistic regression analysis showed that the association between the timing of cranioplasty and unfavorable outcomes was not statistically significant (odds ratio = 1.005, confidence interval 0.997-1.013; p = 0.195). CONCLUSION: The timing of cranioplasty following posttraumatic craniectomy was not related to the neurological outcomes of TBI. Despite the limitations of the retrospective design, the analyses provide preliminary information to elucidate the question.

Surgical and endovascular treatment for ruptured anterior circulation cerebral aneurysms: a comparison of outcomes--a single centre study from Taiwan.

The purpose of this 2-year retrospective study is to compare the outcomes of patients with either surgical clipping or endovascular coiling treatment for ruptured anterior circulation cerebral aneurysms. We enrolled 100 patients with spontaneous subarachnoid hemorrhage resulting from ruptured anterior circulation cerebral aneurysms. We reviewed the demographic information, operative details, and image examinations including computed tomography (CT), digital subtraction angiography, and magnetic resonance imaging of brains. The patients were subdivided into two groups on the basis of treatment modalities: surgical clipping (N = 44) or endovascular coiling (N = 56). The modified Rankin's scale (mRS) was used as an outcome measures. Unfavorable outcome was defined by a mRS score of 1-3. The mean age of 100 patients, comprising 35 men and 65 women, was 57.48 ± 12.68 years. The follow-up period was 18.91 ± 13.05 months in average. The differences between the clipping and coiling groups in terms of admission Glasgow Coma Scale, Hunt and Hess grade, World Federation of Neurosurgical Societies grade, and Fisher's grade by CT scans were not statistically significant. There was no intergroup difference in the following results: symptomatic or radiographic vasospasm, post-treat rebleeding, and recurrence of aneurysms. Although the incidences of unfavorable outcome at the end of follow-up were 32.0% and 27.0% in the clipping and coiling group respectively, it revealed no significant difference (p = 0.202). In dealing with the patients with ruptured anterior circulation cerebral aneurysms, our results provide helpful information when discussing projected outcome before surgical or endovascular treatment.

Bilateral chronic subdural hematoma: what is the clinical significance?

BACKGROUND: Bilateral chronic subdural hematoma (CSDH) is not uncommon, although information on this condition is limited. AIMS: We aim to identify the differences in clinical characteristics between patients with bilateral or unilateral CSDH. METHODS: Ninety-eight patients with CSDH were enrolled in the two-year retrospective study. We investigated neurological outcome, morbidity, mortality, and recurrences after burr hole craniostomy for CSDH. RESULTS: Bilateral convexity hematomas were identified in 25 of 98 CSDH (25.51%). The patients with bilateral lesions had a lower incidence of hemiparesis than those having unilateral lesions (p = 0.004). Analysis of the neuro-images revealed significant differences in the presence of a midline shift (p = 0.001) and thickness of the hematoma (p < 0.001). The mean Markwalder subdural hematoma grade at admission was 1.89 ± 0.66 and 1.64 ± 0.49 in the unilateral and bilateral hematoma groups, respectively (p = 0.010). After a minimum follow-up period of 6 months, the mean Glasgow Outcome Scale was not significantly different (p = 0.060). The recurrence rate of up to 28.00% observed for the bilateral disease was found to be higher than 9.59% observed for the unilateral disease (p = 0.042). CONCLUSION: The frequency of focal neurological deficits was found to be lesser in patients with bilateral CSDH, and it may confound the diagnosis and delay treatment. To prevent neurological deterioration resulting from the thicker hematomas, early surgical decompression for bilateral CSDH should be implemented. Additionally, clinicians must be aware of the higher recurrent rate of bilateral CSDH after burr hole craniostomy.

Thirty-day mortality in traumatically brain-injured patients undergoing decompressive craniectomy.

OBJECT: Decompressive craniectomy is a life-saving measure for patients who have sustained traumatic brain injury (TBI), but patients undergoing this procedure may still die during an early phase of head injury. The aim of this study was to investigate the incidence, causes, and risk factors of 30-day mortality in traumatically brain-injured patients undergoing decompressive craniectomy. METHODS: The authors included 201 head-injured patients undergoing decompressive craniectomy in this 3-year retrospective study. The main outcome evaluated was 30-day mortality in patients who had undergone craniectomy after TBI. Demographic and clinical data, including information on death, were obtained for subsequent analysis. The authors identified differences between survivors and nonsurvivors in terms of clinical parameters; multivariate logistic regression was used to adjust for independent risk factors of short-term death. RESULTS: The 30-day mortality rate was 26.4% in traumatically brain-injured patients undergoing decompressive craniectomy. The majority of deaths following decompression resulted from uncontrollable brain swelling and extensive brain infarction, which accounted for 79.2% of mortality. In the multivariate logistic regression mode, the 2 independent risk factors for 30-day mortality were age (OR 1.035 [95% CI 1.006-1.064]; p = 0.018) and Glasgow Coma Scale (GCS) score before decompressive craniectomy (OR 0.769 [95% CI 0.597-0.990]; p = 0.041). CONCLUSIONS: There is a high 30-day mortality rate in traumatically brain-injured patients undergoing decompressive craniectomy. Most of the deaths are attributed to ongoing brain damage, even after decompression. Risk factors of short-term death, including age and preoperative GCS score, are important in patient selection for decompressive craniectomy, and these factors should be considered together to ensure the highest chance of surviving TBI.

Tracheostomy in craniectomised survivors after traumatic brain injury: a cross-sectional analytical study.

BACKGROUND: Decompressive craniectomy (DC) is a life-saving measure for traumatic brain injury (TBI). However, survivors may remain in a vegetative or minimally conscious state and require tracheostomy to facilitate airway management. In this cross-sectional analytical study, we investigated the predictors for tracheostomy requirement and influence of tracheostomy timing on outcomes in craniectomised survivors after TBI. METHODS: We enrolled 160 patients undergoing DC and surviving >7 days after TBI in this 3-year retrospective study. The patients were subdivided into 2 groups based on whether tracheostomy was (N=38) or was not (N=122) performed. We identified intergroup differences in early clinical parameters. Multivariable logistic regression was used to adjust for independent predictors of the need for tracheostomy. Early tracheostomy was defined as the performance of the procedure within the first 10 days after DC. Intensive care unit (ICU) stay, hospital stay, mortality, and Glasgow outcome scale (GOS) were analysed according to the timing of the tracheostomy procedure. RESULTS: After TBI, 24% of craniectomised survivors required tracheostomy. In the multivariate logistic regression mode, the significant factors related to the need for tracheostomy were age (odds ratio=1.041; p=0.002), the Glasgow coma score (GCS) at admission (odds ratio=0.733; p=0.005), and normal status of basal cisterns (odds ratio=0.000; p=0.008). The ICU stay was shorter for patients with early tracheostomy than for those undergoing late tracheostomy (p=0.004). The timing of tracheostomy had no influence on the hospital stay, mortality, or GOS. CONCLUSION: Age and admission GCS were independent predictors of the need for tracheostomy in craniectomised survivors after TBI. If tracheostomy is necessary, an earlier procedure may assist in patient care.

Remote epidural hemorrhage after unilateral decompressive hemicraniectomy in brain-injured patients.

Epidural hemorrhage (EDH) that develops remote from the decompressed hemisphere can be associated with devastating morbidity after hemicraniectomy for traumatic brain injury (TBI). In this study, we investigated the incidence, risk factors, and outcome influence of post-craniectomy remote EDH. For this retrospective study, we enrolled 139 patients undergoing unilateral hemicraniectomy for TBI. The patients were subdivided into two groups based on whether EDH remote from the site of bone decompression was present (n=11) or not (n=128). We identified the intergroup differences in clinical parameters and outcomes. Multivariate odds regression was used to adjust for independent risk factors of the development of EDH. The incidence of remote EDH following decompressive hemicraniectomy for TBI was 7.9%. There were two independent risk factors for remote EDH, including absence of contusional hemorrhage (odds ratio, 95% confidence interval=6.158, 1.090-34.802; p=0.040) and presence of remote skull fracture (odds ratio, 95% confidence interval=19.770, 2.194-178.152; p=0.008) in preoperative computed tomography scans. The mean Glasgow Outcome Scale did not differ between the patients with and without EDH. In conclusion, remote EDH in patients undergoing unilateral decompressive hemicraniectomy for TBI is not uncommon. The absence of contusional hemorrhage and presence of remote skull fracture are independent risk factors. Although postcraniectomy remote EDH is devastating, timely computed tomography scanning and immediate hematoma evacuation are efficient and crucial for patient outcomes.

Chemical models and their mechanistic implications for the transformation of 6-cyanouridine 5'-monophosphate catalyzed by orotidine 5'-monophosphate decarboxylase.

The reactions of 6-cyano-1,3-dimethyluracil have been studied as chemical models to illustrate the mechanism for the transformation of 6-cyanouridine 5'-monophosphate (6-CN-UMP) to barbiturate ribonucleoside 5'-monophosphate (BMP) catalyzed by orotidine 5'-monophosphate decarboxylase (ODCase). The results suggest that the Asp residue in the ODCase active site plays the role of a general base in the transformation.

Chemical models and their mechanistic implications for the transformation of 6-cyanouridine 5'-monophosphate catalyzed by orotidine 5'-monophosphate decarboxylase.

Orotidine 5'-monophosphate decarboxylase (ODCase) catalyzes an unprecedented transformation of 6- cyanouridine 5'-monophosphate (6-CN-UMP) into barbiturate nucleoside 5'-monophosphate (6-hydroxyuridine 5'-monophosphate, BMP). The reactions of 6- cyano-1,3-dimethyluracil toward various nucleophilic conditions have been studied as chemical models in order to understand the possible mechanism for the ODCase-catalyzed transformation of 6-CN-UMP.