Neuronal Specific Increase of Phosphatidylserine by Docosahexaenoic Acid

Phosphatidylserine (PS), the major acidic phospholipid class in eukaryotic biomembranes, plays an important role in various signaling pathways. We have previously demonstrated that docosahexaenoic acid (DHA, 22:6n-3) positively modulates PS biosynthesis and accumulation in neuronal cells, promoting survival. In this paper, we demonstrate that the increase of PS levels upon DHA enrichment is not a universal mechanism, but specific to neuronal cells. When cells were enriched with 20 muM DHA, 18:0, 22:6-PS increased in both neuronal (Neuro 2A) and non-neuronal cells (Chinese hamster ovary K1 cells, NIH-3T3, and human embryonic kidney cells). However, the increase of the total PS level was observed only in Neuro 2A cells because of the fact that other PS species, such as 18:0, 18:1-PS and 18:1, 18:1-PS decreased significantly in non-neuronal cells, compensating for the increase of 18:0, 22:6-PS. DHA enrichment did not affect the messenger RNA levels of PS synthase 1 (PSS1) and PSS2. Over-expression of genes encoding PSS1 or PSS2 altered neither the PS level nor the effect of DHA on PS increase in both neuronal and non-neuronal cells. From these results, it is concluded that the PS increase by DHA, specifically observed in neuronal cells, may represent a unique mechanism for expanding the PS pool so far known in mammalian cells.     

An unceasing problem: soil-transmitted helminthiases in rural Malaysian communities

Despite great development in socioeconomic status throughout 50 years of independence, Malaysia is still plagued with soil-transmitted helminthiases (STH). STH continue to have a significant impact on public health particularly in rural communities. In order to determine the prevalence of STH among rural Orang Asli children and to investigate the possible risk factors affecting the pattern of this prevalence, fecal samples were collected from 292 Orang Asli primary schoolchildren (145 males and 147 females) age 7-12 years, from Pos Betau, Kuala Lipis, Pahang. The samples were examined by Kato-Katz and Harada Mori techniques. Socioeconomic data were collected using pre-tested questionnaires. The overall prevalence of ascariasis, trichuriasis, and hookworm infections were 67.8, 95.5 and 13.4%, respectively. Twenty-nine point eight percent of the children had heavy trichuriasis, while 22.3% had heavy ascariasis. Sixty-seven point seven percent of the children had mixed infections. Age > 10 years (p = 0.016), no toilet in the house (p = 0.012), working mother (p = 0.040), low household income (p = 0.033), and large family size (p = 0.028) were identified as risk factors for ascariasis. Logistic regression confirmed low income, no toilet in the house and working mother as significant risk factors for ascariasis. The prevalence of STH is still very high in rural Malaysian communities. STH may also contribute to other health problems such as micronutrient deficiencies, protein-energy malnutrition and poor educational achievement. Public health personnel need to reassess current control measures and identify innovative and integrated ways in order to reduce STH significantly in rural communities.     

Chylous Ascites Secondary to Pancreatitis: Management of an Uncommon Entity Using Parenteral Nutrition and Octreotide

Malignancy, surgical trauma, cirrhosis and tuberculosis account for more than 95% of causes for chylous ascites. We report a case of persistent chylous ascites following acute pancreatitis that responded to parenteral nutrition and octreotide. A 50 year-old male was diagnosed with acute alcoholic pancreatitis after presenting with typical abdominal pain, and elevated amylase and lipase. The acute symptoms resolved within one week. Four weeks later he started developing increased abdominal girth. Examination revealed the presence of shifting dullness and paracentesis confirmed diagnosis of chylous ascites. Investigations for the common causes of chylous ascites were negative. Laparoscopy confirmed the presence of fat necrosis within mesenteric lymph nodes linking the chylous ascites to the episode of pancreatitis. The Chylous ascites was resistant to the usual medical therapy, but responded only to the combination of octreotide and total parenteral nutrition with complete resolution of ascites in 8 weeks. This case of chylous ascites secondary to pancreatitis represents an uncommon presentation with effective management resulting in a dramatic response.     

Primary Nocardia meningitis in a patient without a predisposing condition: case report and review of the literature

A case of primary Nocardia meningitis in a patient without a predisposing condition is presented and 4 other reported cases are reviewed. The presenting features were fever, headache, altered consciousness, and neck stiffness. Cerebrospinal fluid examination (CSF) revealed hypoglycorrhachia (<40 mg/dl), elevated protein (>100 mg/dl), and pleocytosis with predominant neutrophils in all patients. Culture of CSF was positive for Nocardia in 4 of the 5 patients. Mortality was 50%. Diagnosis was frequently delayed and this probably contributed to the high mortality. Compared with Nocardia meningitis in association with a predisposing condition, primary Nocardia meningitis without a predisposing condition has similar clinical features and outcome.     

A connecting hinge represses the activity of endothelial nitric oxide synthase

In mammals, endothelial nitric oxide synthase (eNOS) has the weakest activity, being one-tenth and one-sixth as active as the inducible NOS (iNOS) and the neuronal NOS (nNOS), respectively. The basis for this weak activity is unclear. We hypothesized that a hinge element that connects the FMN module in the reductase domain but is shorter and of unique composition in eNOS may be involved. To test this hypothesis, we generated an eNOS chimera that contained the nNOS hinge and two mutants that either eliminated (P728IeNOS) or incorporated (I958PnNOS) a proline residue unique to the eNOS hinge. Incorporating the nNOS hinge into eNOS increased NO synthesis activity 4-fold, to an activity two-thirds that of nNOS. It also decreased uncoupled NADPH oxidation, increased the apparent K(m)O(2) for NO synthesis, and caused a faster heme reduction. Eliminating the hinge proline had similar, but lesser, effects. Our findings reveal that the hinge is an important regulator and show that differences in its composition restrict the activity of eNOS relative to other NOS enzymes.     

EUS-guided FNA diagnostic yield of malignancy in solid pancreatic masses: a benchmark for quality performance measurement

BACKGROUND: The diagnostic yield of EUS-guided FNA (EUS-FNA) of solid pancreatic masses is a potential benchmark for EUS-FNA quality, because the majority of EUS-FNA of solid pancreatic masses should be diagnostic for malignancy. OBJECTIVES: To determine the cytologic diagnostic rate of malignancy in EUS-FNA of solid pancreatic masses and to determine if variability exists among endoscopists and centers. DESIGN: Multicenter retrospective study. PATIENTS: EUS centers provided cytology reports for all EUS-FNAs of solid, noncystic, >or=10-mm-diameter, solid pancreatic masses during a 1-year period. MAIN OUTCOME MEASUREMENT: Cytology diagnostic of pancreatic malignancy. RESULTS: A total of 1075 patients underwent EUS-FNA at 21 centers (81% academic) with 41 endoscopists. The median number of EUS-FNA of solid pancreatic masses performed during the year per center was 46 (range, 4-177) and per endoscopist was 19 (range, 1-97). The mean mass dimensions were 32 x 27 mm, with 73% located in the head. The mean number of passes was 3.5. Of the centers, 90% used immediate cytologic evaluation. The overall diagnostic rate of malignancy was 71%, 95% confidence interval 0.69%-0.74%, with 5% suspicious for malignancy, 6% atypical cells, and 18% negative for malignancy. The median diagnostic rate per center was 78% (range, 39%-93%; 1st quartile, 61%) and per endoscopist was 75% (range, 0%-100%; 1st quartile, 52%). LIMITATIONS: Retrospective study, participation bias, and varying chronic pancreatitis prevalence. CONCLUSIONS: (1) EUS-FNA cytology was diagnostic of malignancy in 71% of solid pancreatic masses and (2) endoscopists with a final cytologic diagnosis rate of malignancy for EUS-FNA of solid masses that was less than 52% were in the lowest quartile and should evaluate reasons for their low yield.     

Characterization of a Plasmodium falciparum macrophage-migration inhibitory factor homologue

BACKGROUND: Macrophage-migration inhibitory factor (MIF), one of the first cytokines described, has a broad range of proinflammatory properties. The genome sequencing project of Plasmodium falciparum identified a parasite homologue of MIF. The protein is expressed during the asexual blood stages of the parasite life cycle that cause malarial disease. The identification of a parasite homologue of MIF raised the question of whether it affects monocyte function in a manner similar to its human counterpart. METHODS: Recombinant P. falciparum MIF (PfMIF) was generated and used in vitro to assess its influence on monocyte function. Antibodies generated against PfMIF were used to determine the expression profile and localization of the protein in blood-stage parasites. Antibody responses to PfMIF were determined in Kenyan children with acute malaria and in control subjects. RESULTS: PfMIF protein was expressed in asexual blood-stage parasites, localized to the Maurer's cleft. In vitro treatment of monocytes with PfMIF inhibited random migration and reduced the surface expression of Toll-like receptor (TLR) 2, TLR4, and CD86. CONCLUSIONS: These results indicate that PfMIF is released during blood-stage malaria and potentially modulates the function of monocytes during acute P. falciparum infection.     

Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone

Indian hedgehog (Ihh) is essential for chondrocyte and osteoblast proliferation/differentiation during prenatal endochondral bone formation. The early lethality of various Ihh-ablated mutant mice, however, prevented further analysis of its role in postnatal bone growth and development. In this study, we describe the generation and characterization of a mouse model in which the Ihh gene was successfully ablated from postnatal chondrocytes in a temporal/spatial-specific manner; postnatal deletion of Ihh resulted in loss of columnar structure, premature vascular invasion, and formation of ectopic hypertrophic chondrocytes in the growth plate. Furthermore, destruction of the articular surface in long bones and premature fusion of growth plates of various endochondral bones was evident, resulting in dwarfism in mutant mice. More importantly, these mutant mice exhibited continuous loss of trabecular bone over time, which was accompanied by reduced Wnt signaling in the osteoblastic cells. These results demonstrate, for the first time, that postnatal chondrocyte-derived Ihh is essential for maintaining the growth plate and articular surface and is required for sustaining trabecular bone and skeletal growth.