Amide proton transfer and chemical exchange saturation transfer MRI differentiates between growing and non-growing intracranial meningiomas: a pilot study.

AIM: To differentiate between growing and non-growing intracranial meningiomas using magnetisation transfer ratio (MTR) values with amide proton transfer (APT) and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventeen patients with suspected intracranial meningiomas who underwent APT-CEST MRI from November 2020 to April 2021 were evaluated retrospectively. MTR values on APT-CEST imaging as well as conventional MRI features were evaluated. These parameters were compared in growing meningiomas versus non-growing meningiomas and the findings compared with previous MRI examinations. ROC curve analysis was also performed to determine the diagnostic cut-offs for MTR. RESULTS: The cohort comprised 10 patients with growing meningiomas (two men [20%], eight women [80%]; mean age [standard deviation (SD)]: 59.9 years [16]) and seven patients with non-growing meningiomas (seven women [100%]; mean age [SD]: 63.9 years [18.6]). Significant differences were found in MTR values (0.0198 ± 0.0003 versus 0.0131 ± 0.0002; p<0.0001) between the growing meningiomas and non-growing meningiomas groups, respectively. The receiver operating characteristic (ROC) curve analysis showed that MTR values clearly differentiated between growing and non-growing meningiomas. At an area under the ROC curve (AUC) threshold of 0.0151, diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTR were 100%, 85.7%, 90.9%, and 100%, respectively. CONCLUSION: Patients with growing meningiomas could be discriminated from patients with non-growing meningiomas, using the MTR values on post-growth tumour APT-CEST imaging.

Interleukin-18 is associated with the presence of interstitial lung disease in rheumatoid arthritis: a cross-sectional study.

OBJECTIVE: Serum interleukin-18 (IL-18) levels are increased in patients with interstitial lung disease (ILD). In addition, IL-18 levels are increased in patients with rheumatoid arthritis (RA) and are associated with arthritis activity. We determined whether increased IL-18 levels are associated with ILD in RA. METHOD: RA patients were enrolled using an RA cohort database. Plasma IL-18 levels were measured by enzyme-linked immunosorbent assay. ILD was determined by a pulmonologist and a radiologist based on chest radiography and computed tomography findings. IL-18 levels for RA with ILD and RA without ILD were compared. Associations between ILD and various markers including IL-18 and confounding factors (e.g. smoking history) were investigated by logistic regression analysis. Diagnostic values of IL-18 for the presence of ILD were investigated using receiver operating characteristics curve analysis. RESULTS: ILD was complicated in 8.2% (n = 26) of the study population (N = 312). Plasma IL-18 levels were higher for RA patients with ILD than for RA patients without ILD (721.0 ± 481.4 vs 436.8 ± 438.9 pg/mL, p < 0.001). IL-18, Krebs von den Lungen-6, and anti-cyclic citrullinated peptide antibody titre and glucocorticoid doses were independently associated with the presence of ILD during multivariate logistic regression analysis. Sensitivity and specificity of IL-18 levels for the detection of ILD in RA patients were 65.3% and 76.3%, respectively (area under the curve = 0.73). CONCLUSION: Plasma IL-18 levels were higher for RA patients with ILD than for those without ILD. Increased IL-18 levels were associated with the presence of ILD.

Pathogenic factors in Candida biofilm-related infectious diseases.

Candida albicans is a commonly found member of the human microflora and is a major human opportunistic fungal pathogen. A perturbation of the microbiome can lead to infectious diseases caused by various micro-organisms, including C. albicans. Moreover, the interactions between C. albicans and bacteria are considered to play critical roles in human health. The major biological feature of C. albicans, which impacts human health, resides in its ability to form biofilms. In particular, the extracellular matrix (ECM) of Candida biofilm plays a multifaceted role and therefore may be considered as a highly attractive target to combat biofilm-related infectious diseases. In addition, extracellular DNA (eDNA) also plays a crucial role in Candida biofilm formation and its structural integrity and induces the morphological transition from yeast to the hyphal growth form during C. albicans biofilm development. This review focuses on pathogenic factors such as eDNA in Candida biofilm formation and its ECM production and provides meaningful information for future studies to develop a novel strategy to battle infectious diseases elicited by Candida-formed biofilm.

Evaluation of the effectiveness of the potent bis-quaternary ammonium compound, 4,4'-(α,ω-hexametylenedithio) bis (1-octylpyridinium bromide) (4DTBP-6,8) on Pseudomonas aeruginosa.

AIMS: Quaternary ammonium compounds (QACs), including benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC) are cationic surfactants and have been used widely as general disinfectants in the medical field due to their strong antibacterial effects and low cytotoxicity to human cells. 4,4'-(α,ω-hexametylenedithio) bis (1-octylpyridinium bromide) (4DTBP-6,8) is one of the potent bis-QACs synthesized to improve the antimicrobial activities of mono-QACs such as BAC. This study aimed to assess the effectiveness of 4DTBP-6,8 against Pseudomonas aeruginosa, a prevalent hospital pathogen. METHODS AND RESULTS: The minimum inhibitory concentrations of 4DTBP-6,8, CPC and BAC against P. aeruginosa were measured. 4DTBP-6,8 exhibited strong antibacterial activity. We assessed the bactericidal effects of QACs against P. aeruginosa under certain conditions and their cytotoxicities in human epithelial cells using lactate dehydrogenase (LDH) release. 4DTBP-6,8 exerted excellent bactericidal effects against high concentrations of bacteria, biofilm cells and even in the presence of contaminated proteins. Cellular LDH was not released by the treatment with 4DTBP-6,8. CONCLUSIONS: 4DTBP-6,8 exhibited the strongest bactericidal activity against P. aeruginosa among the three QACs tested without any cytotoxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: The potent bis-QAC, 4DTBP-6,8 has the potential to be an effective disinfectant in preventing hospital infections caused by P. aeruginosa.

Novel reuterin-related compounds suppress odour by periodontopathic bacteria.

OBJECTIVE: Halitosis is caused by volatile sulphur compounds including methyl mercaptan (CH3 SH) in the oral cavity and is a serious problem that limits interpersonal social communication. The aim of study was to evaluate the effects of reuterin-related compounds (RRCs) on halitosis-related periodontopathic bacteria in vitro. MATERIALS AND METHODS: RRC-01, RRC-02 and RRC-03 (32 and 64 µg ml-1 ) in culture media containing Fusobacterium nucleatum JCM8523 and Porphyromonas gingivalis ATCC33277 were used. The effects of RRCs on CH3 SH production and detectable odour by F. nucleatum and P. gingivalis were examined by CH3 SH production assay and organoleptic test, respectively. The number of bacterial cells was also measured using an ATP assay. In P. gingivalis treated with RRCs, the expression of mgl gene, which is responsible for CH3 SH production, was examined by qRT-PCR. RESULTS: CH3 SH production and the score of detectable odour from F. nucleatum and P. gingivalis culture media containing RRCs were significantly lower than that without RRCs (P < 0.05). The expression of mgl gene in P. gingivalis was significantly downregulated by RRC-01 (P < 0.01), but not by RRC-02 or RRC-03. CONCLUSIONS: RRCs are potent oral care products for preventing halitosis via reducing CH3 SH production.

IDENTICAL TWIN SISTERS WITH CLOSE ONSET OF GRAVES' DISEASE AND WITH MULTIPLE HLA SUSCEPTIBILITY ALLELES FOR GRAVES' DISEASE.

CONTEXT: Autoimmune thyroid disease is considered a multifactorial disorder in which autoimmunity against thyroid antigens is facilitated by exposure to endogenous and environmental factors. We present here a rare case of identical female twins who developed consecutively Graves' disease within a few months and had three HLA susceptibility alleles for the development of Graves' disease. SUBJECTS: A 28-year-old woman was referred to our hospital complaining of thirst, sweating, palpitations, tremor and skin rash. Laboratory data showed hyperthyroidism with antibodies against the thyroid stimulating hormone receptor and ultrasonography of the thyroid revealed enlargement with hypervascularity. Her identical twin was referred to our hospital because of similar symptoms. RESULT: We diagnosed them with Graves' disease and both were treated with methimazole. Human leukocyte antigen genotyping showed that both twins possessed the DRB1*04:05, DQB1*04:01:01, DPB1*05:01 haplotype, which confers susceptibility to Graves' disease. CONCLUSIONS: This case supports the hypothesis that interaction of multiple human leukocyte antigen susceptibility alleles as well as genetic background and environmental factors might synergistically contribute the close timing in Graves' disease onset.

Effect of aerobic exercise training followed by a low-calorie diet on metabolic syndrome risk factors in men.

BACKGROUND AND AIMS: Whether low-volume, high-intensity, interval training (HIIT) is an adequate exercise method for improving metabolic risk factors is controversial. Moreover, it is not known if performing a short-term, low-calorie diet intervention (LCDi) after a HIIT program affects risk factors. This study investigated how an 8-week, 3 times/week exercise intervention (EXi) incorporating either HIIT or moderate-intensity continuous training (MICT) followed by a 4-week LCDi affects risk factors. METHODS AND RESULTS: Twenty-six male workers with metabolic risk factors (47.4 ± 7.1 years; cardiorespiratory capacity (VO2peak) of 28.5 ± 3.9 ml/kg/min) were randomly assigned to either the HIIT (3 sets of 3-min cycling with a 2-min active rest between sets, 180 kcal) or MICT (45 min, 360 kcal) group. After the EXi, all subjects participated in a 4-week LCDi (4 counseling sessions). During the EXi, VO2peak improved more (P < 0.05) through HIIT (25.4 ± 14.6%) than through MICT (14.9 ± 12.8%), whereas improvements in body fat and HDL cholesterol were similar. During the LCDi, some risk factors improved further (P < 0.05) without any group differences, while VO2peak in the HIIT group decreased (P < 0.05) to the same level as in the MICT group. CONCLUSION: VO2peak increased more with HIIT than with MICT during the EXi despite HIIT having a lower exercise volume than MICT, but this advantage of HIIT promptly disappeared through detraining. An intervention strategy consisting of 8 weeks of either HIIT or MICT followed by a 4-week LCDi has a positive effect on metabolic risk factors. CLINICAL TRIAL REGISTRATION: UMIN11352.

Catechins inhibit vascular endothelial growth factor production and cyclooxygenase-2 expression in human dental pulp cells.

AIM: To investigate the effect of catechins on vascular endothelial growth factor (VEGF) production and cyclooxygenase-2 (COX-2) expression in human dental pulp cells (HDPC) stimulated with bacteria-derived factors or pro-inflammatory cytokines. METHODOLOGY: Morphologically fibroblastic cells established from explant cultures of healthy human dental pulp tissues were used as HDPC. HDPC pre-treated with catechins, epigallocatechin-3-gallate (EGCG) or epicatechin gallate (ECG), were exposed to lipopolysaccharide (LPS), peptidoglycan (PG), interlukin-1ß (IL-1ß) or tumour necrosis factor-α (TNF-α). VEGF production was examined by enzyme-linked immunosorbent assay, and COX-2 expression was assessed by immunoblot. RESULTS: EGCG and ECG significantly reduced LPS- or PG-mediated VEGF production in the HDPC in a dose-dependent manner. EGCG also prevented IL-1ß-mediated VEGF production. Although TNF-α did not enhance VEGF production in the dental pulp cells, treatment of 20 µg mL(-1) of EGCG decreased the level of VEGF. In addition, the catechins attenuated COX-2 expression induced by LPS and IL-1ß. CONCLUSIONS: The up-regulated VEGF and COX-2 expressions in the HDPC stimulated with these bacteria-derived factors or IL-1ß were diminished by the treatment of EGCG and ECG. These findings suggest that the catechins may be beneficial as an anti-inflammatory tool of the treatment for pulpal inflammation.

Effects of extracellular DNA from Candida albicans and pneumonia-related pathogens on Candida biofilm formation and hyphal transformation.

AIMS: The aim of this study was to investigate the effects of genomic DNA purified from Candida albicans and pneumonia-related pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, on in vitro biofilm formation and morphological change of 3 Candida species (C. albicans, C. glabrata, and C. tropicalis). METHODS AND RESULTS: Biofilm formation was evaluated by the crystal violet assay and colony-forming unit counts. Morphological characteristics of biofilms were evaluated by scanning electron microscopy and fluorescence microscopy. Addition of DNA at a low concentration (<1·0 µg ml(-1)) significantly increased biofilm mass of all three Candida species. In contrast, the addition of DNA at a high concentration (10 µg ml(-1)) decreased the biofilm mass. Interestingly, the formation of hyphae in a dense network of yeast cells was observed in C. albicans biofilms exposed to a low concentration of DNA (<1·0 µg ml(-1)). CONCLUSIONS: These findings demonstrated that extracellular DNA (eDNA) plays a crucial role in Candida biofilm formation and suggested that eDNA may induce the morphological transition from yeast to hyphal growth form during C. albicans biofilm development. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel therapy targeting eDNA may be applicable for Candida infection to decrease biofilm formation and hyphal formation.

Clinical usefulness of concentrated ascites reinfusion therapy (CART) for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis.

PURPOSE: Cell-free and concentrated ascites reinfusion therapy (CART) is intended to treat patients by ultrafiltration and reinfusion of their refractory ascites. In the CART system, bacteria and cancer cells in removed massive ascites are filtrated. Then, water is removed in the condenser, resulting in a higher protein concentration. The purpose of this study was to assess the clinical usefulness of CART in the treatment of refractory massive ascites in patients with cancerous peritonitis. MATERIALS AND METHODS: CART was performed 13 times in four patients with ovarian and endometrial cancer. RESULTS: Autologous protein with a higher concentration was intravenously administered. The amount of aspirated and condensed ascites was 3,190 +/- 1,086 ml (975 4,500 ml) and 538 +/- 249 ml (100 - 860 ml), respectively. Condensed albumin, albumin concentration, and concentration time were 43.2 +/- 25.8 g, 8.2 +/- 3.3 g/dl, and 73.3 +/- 24.8 min (28 - 122 min), respectively. CART was effective in maintaining serum albumin concentrations, and it is possible to repeat infusion. During CART, patients performance status was 1-2 and vital signs were stable except for mild elevations in body temperature. Daily life was maintained without serious side-effects. CONCLUSIONS: The use of CART for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis contributes to improvements in quality of life and relief of symptoms. With autologous infusion of condensed ascites, patients can avoid infection, allergic reactions, and administration of expensive blood products.

Effects of extracellular DNA and DNA-binding protein on the development of a Streptococcus intermedius biofilm.

AIMS: The aim of this study was to clarify the effects of homologous and heterologous extracellular DNAs (eDNAs) and histone-like DNA-binding protein (HLP) on Streptococcus intermedius biofilm development and rigidity. METHODS AND RESULTS: Formed biofilm mass was measured with 0·1% crystal violet staining method and observed with a scanning electron microscope. The localizations of eDNA and extracellular HLP (eHLP) in formed biofilm were detected by staining with 7-hydoxyl-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) and anti-HLP antibody without fixation, respectively. DNase I treatment (200 U ml(-1)) markedly decreased biofilm formation and cell density in biofilms. Colocalization of eHLP and eDNA in biofilm was confirmed. The addition of eDNA (up to 1 µg ml(-1)) purified from Strep. intermedius, other Gram-positive bacteria, Gram-negative bacteria, or human KB cells into the Strep. intermedius culture increased the biofilm mass of all tested strains of Strep. intermedius, wild-type, HLP-downregulated strain and control strains. In contrast, the addition of eDNA (>1 µg ml(-1)) decreased the biofilm mass of all Strep. intermedius strains. CONCLUSIONS: These findings demonstrated that eDNA and eHLP play crucial roles in biofilm development and its rigidity. SIGNIFICANCE AND IMPACT OF THE STUDY: eDNA- and HLP-targeting strategies may be applicable to novel treatments for bacterial biofilm-related infectious diseases.

Mosquitoes and other aquatic insects in fallow field biotopes and rice paddy fields.

Fallow field biotopes that develop from abandoned rice fields are man-made wetlands that provide new habitats for various aquatic animals. Although consideration of such biotopes generally focuses on their positive aspects, this study evaluated the negative aspects of establishing fallow field biotopes with regard to mosquito breeding sites. To determine whether fallow field biotopes become breeding habitats for vector mosquitoes, we evaluated mosquito fauna in fallow field biotopes and adjacent rice fields. We found larvae of Anopheles lesteri, Anopheles sinensis and Culex tritaeniorhynchus (all: Diptera: Culicidae) in the biotopes. Although abundances of mosquito larvae in the biotopes and rice fields were statistically similar, mosquito abundances in rice fields increased dramatically in August when the water level reduced after the rainy season. The abundance and variety of the mosquitoes' natural predators were greater in biotopes than in rice fields because the former are a permanent and stable aquatic environment. A generalized linear mixed model showed a negative effect of predator diversity on mosquito larvae abundance in both habitats. Although fallow field biotopes become breeding habitats for vector mosquitoes, establishing biotopes from fallow fields in order to protect various aquatic animals, including mosquito insect predators, may help to control mosquito breeding.

A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells.

The rat small eye strain (rSey) lacks eyes and nose in the homozygote, and is similar to the mouse Sey strain with mutations in the Pax-6 gene. We isolated Pax-6 cDNA clones from an rSey homozygote library, and found an internal deletion of about 600 basepairs in the serine/threonine-rich domain. At the genomic level, a single base (G) insertion in an exon generates an abnormal 5' donor splice site, thereby producing the truncated mRNA. Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain.

Irsogladine maleate regulates epithelial barrier function in tumor necrosis factor-α-stimulated human gingival epithelial cells.

BACKGROUND AND OBJECTIVE: As epithelial cells function as a mechanical barrier, the permeability of the gingival epithelial cell layer indicates a defensive capability against invasion by periodontal pathogens. We have reported the expression of claudin-1 and E-cadherin, key regulators of permeability, in the gingival junctional epithelium. Irsogladine maleate (IM) is a medication for gastric ulcers and also regulates Aggregatibacter actinomycetemcomitans-stimuated chemokine secretion and E-cadherin expression in gingival epithelium. In this study, we have further investigated the effects of IM on the barrier functions of gingival epithelial cells under inflammatory conditions. MATERIAL AND METHODS: We examined the permeability, and the expression of claudin-1 and E-cadherin, in human gingival epithelial cells (HGECs) stimulated with tumor necrosis factor (TNF)-α, with or without IM. RESULTS: TNF-α increased the permeability of HGECs, and IM abolished the increase. TNF-α reduced the expression of E-cadherin in HGECs, and IM reversed the reduction. In addition, immunofluorescence staining showed that TNF-α disrupted claudin-1 expression in HGECs, and IM reversed this effect. CONCLUSION: The results suggest that IM reverses the TNF-α-induced disruption of the gingival epithelial barrier by regulating E-cadherin and claudin-1.

Bactericidal activity and oral pathogen inactivation by electromagnetic wave irradiation.

AIMS: The aim of this work was to clarify the effects of electromagnetic wave irradiation (EMWI) on oral bacterial pathogens. METHODS AND RESULTS: A Gram-negative (Porphyromonas gingivalis) or Gram-positive (Streptococcus mutans, S. intermedius, Enterococcus faecalis) bacterial suspension was irradiated by EMW apparatus (500-1000 kHz, 5-15 times, 1 s time(-1) ). Quantification of survival bacteria by CFU counting revealed that EMWI exhibited marked bactericidal activity against all tested bacteria and bactericidal activity at 500 kHz increased in an irradiation number-dependent manner. After EMWI at 500 kHz, scanning electron microscopic observations showed that the chain of S. mutans cells was shortened after 5 irradiations and the outlines of bacterial cells (S. mutans and P. gingivalis) were unclear after 5-10 irradiations. EMWI inhibited the inductive effect of S. mutans on pro-inflammatory cytokine production in human monocytes and this inhibitory effect was comparable with that of heat-killed bacteria. Furthermore, using an enzyme activity assay, EMWI partially inactivated the activities of gingipains from P. gingivalis. CONCLUSIONS: These findings demonstrated that EMWI has inactivation and bactericidal activities against single microbial species among four kinds of oral pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Electromagnetic wave irradiation may be applicable for medical disinfection and sterilization, such as refractory periapical periodontitis.

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

BACKGROUND: Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. METHODS: The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. RESULTS: A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. CONCLUSION: Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Long-term stable obesity increases risk of hypertension.

OBJECTIVES: Although some prospective cohort studies have shown that baseline BMI is positively associated with a future incident risk for hypertension, these studies do not account for weight changes during the observation period. Therefore, it is not evident whether future incident risk for hypertension in obese, non-hypertensive people increases when their weight remains stable. We examined the association between long-term weight stability and risk for developing hypertension. METHODS: A total of 5201 Japanese male workers aged 30-59 years underwent health checkups in 2002 and were followed through 2006. To consider transitions in covariates during the follow-up period, we used a time-dependent covariate Cox proportional hazard model to compute the relative risks (RRs) of incident hypertension. Furthermore, as a complementary analysis, we restricted the data to individuals whose BMI remained unchanged (± 5% of baseline BMI) during the follow-up and compared the RRs between BMI categories. RESULTS: During the follow-up, there were 899 newly diagnosed cases of hypertension among the 5201 men (14,888 person-years). Mean change in BMI during the follow-up period of all subjects was 0.2 ± 1.1 kg/m(2) (range: -6.6 to 6.3 kg/m(2)). The multivariate RRs for hypertension increased as BMI increased when we applied the time-dependent covariate Cox proportional hazard model. The complementary analysis showed that the multivariate RR (confidence interval) within the ≥ 27.0 kg/m(2) BMI category was 1.43 (1.16-1.77) times higher than the reference of 23.0-24.9 kg/m(2), whereas the RR for the <21.0 kg/m(2) BMI category was 0.63 (0.51-0.79) times lower than the reference. CONCLUSIONS: A higher baseline BMI increases future incident risk for hypertension even when there has been no major weight increase. Weight management should be encouraged for obese, non-hypertensive people to prevent future hypertension.

The PX domains of p47phox and p40phox bind to lipid products of PI(3)K.

PX domains are found in a variety of proteins that associate with cell membranes, but their molecular function has remained obscure. We show here that the PX domains in p47phox and p40phox subunits of the phagocyte NADPH oxidase bind to phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P(2)) and phosphatidylinositol-3-phosphate (PtdIns(3)P), respectively. We also show that an Arg-to-Gln mutation in the PX domain of p47phox, which is found in patients with chronic granulomatous disease, eliminates phosphoinositide binding, as does the analogous mutation in the PX domain of p40phox. The PX domain of p40phox localizes specifically to PtdIns(3)P-enriched early endosomes, and this localization is disrupted by inhibition of phosphoinositide-3-OH kinase (PI(3)K) or by the Arg-to-Gln point mutation. These findings provide a molecular foundation to understand the role of PI(3)K in regulating neutrophil function and inflammation, and to identify PX domains as specific phosphoinositide-binding modules involved in signal transduction events in eukaryotic cells.

Evaluation of seminal zinc levels by atomic absorption in men with spinal cord injury.

STUDY DESIGN: A case-control study evaluating seminal zinc level in spinal cord injury (SCI) patients. OBJECTIVES: Patients with SCI have neurological prostate dysfunction. There are only some indications in the literature that seminal zinc level may be lower in these patients. Seminal zinc is mainly produced by the prostate and, therefore, can be considered to be a marker of prostate function. The objective of the present study was to determine whether SCI can induce changes in seminal zinc levels and to compare the results with those obtained for normal men (controls). SETTING: The study was carried out in Brazil. METHODS: A total of 24 men with SCI (mean age±s.d. 36.25±10.24 years) and 24 controls (mean age±s.d. 36.50±10.31 years) were studied. Blood and semen were collected after 3 days of abstinence from ejaculation. Semen was left at room temperature for 15 min, stored in liquid nitrogen, and lyophilized. Seminal zinc was determined by atomic absorption. Blood was stored at a controlled temperature of - 70 to -79 °C and later used for the determination of testosterone, prolactin and total prostate-specific antigen using an AxSYM apparatus and Abbott reagents. RESULTS: Mean seminal zinc concentration was 85.20 mg l(-1) for the patients, a lower value than that obtained for the controls (147.16 mg l(-1)) (P=0.0035). CONCLUSION: Patients with SCI have a significant reduction of seminal zinc.

An increase in high-density lipoprotein cholesterol after weight loss intervention is associated with long-term maintenance of reduced visceral abdominal fat.

OBJECTIVES: It is generally agreed that excess abdominal fat, in particular visceral abdominal fat (VAF), is related to an increased risk for obesity-related complications. We examined the association between metabolic risk factors and maintaining VAF after weight loss intervention. METHODS: A total of 54 postmenopausal, obese women who achieved a VAF loss of at least 10% from their baseline values during a 14-week intervention were enrolled as subjects. Body weight, VAF assessed by CT scans, and metabolic risk factors (that is, blood pressure, lipids and glucose) were measured at baseline (week 0), post-intervention (week 15), and at a 2-year follow-up (week 105). The subjects were divided into two groups according to their changes in VAF between weeks 15 and 105 (follow-up period): (1) VAF gainers (VAF changes > 0 cm², n=28) or (2) VAF maintainers (VAF changes ≤ 0 cm², n=26). RESULTS: The mean change in VAF of all subjects during the 14-week intervention was -34±16 cm² (-29.7±12.3%) (P<0.01). Along with this change, improvements (P<0.05) were observed in all metabolic risk factors except for high-density lipoprotein cholesterol (HDLC). During the follow-up period, there were interactions between the two VAF groups in HDLC, triglycerides (TG) and total cholesterol (TC)/HDLC ratio (all P<0.01). In particular, the HDLC of VAF maintainers improved, and the value at week 105 exceeded baseline level (P<0.01). However, systolic and diastolic blood pressure, TC and low-density lipoprotein cholesterol in the VAF maintainers increased (all P<0.05) back to their mean baseline level despite a further decrease in their VAF during the follow-up period (P<0.01). CONCLUSIONS: This study shows that long-term maintenance of VAF after weight loss intervention is associated with improvements in HDLC and TG among obese, postmenopausal women.