Transcriptome profiling reveals sex-specific gene expressions in pupal and adult stages of the mosquito Culex pipiens.

Understanding the development process of male and female mosquitoes provides important basic information for sterile insect release programmes and is important for improving other vector control strategies. However, little is known about the molecular mechanisms that distinguish male from female-specific developmental processes in this species. We used IlluminaRNA-seq to identify sex-specific genes during pupal and adult stages. One hundred and forty-seven genes were expressed only in pupal males, 56 genes were expressed in adult males and another 82 genes were commonly expressed in both male samples. In addition, 26 genes were expressed only in the pupal females, 163 genes were found in the adult females and only one gene was expressed in both female samples. A further quantitative real-time PCR validation of selected genes from the RNA sequencing (RNA-seq) analysis confirmed upregulation of those genes in a sex-specific manner, including: fibrinogen and fibronectin, a zinc finger protein, phospholipase A(2) and a serine protein for female pupae; venom allergen 3, a perlecan, testis-specific serine/threonine-protein kinase 1, testis-specific serine/threonine-protein kinase 6 and cytochrome c-2 for male pupae; a salivary protein, D7 protein precursor, trypsin 7 precursor, D7 protein and nanos for female adults; and tetraspanin F139, cytosol aminopeptidase, testis-specific serine/threonine-protein kinase 1, a testis-specific serine/threonine-protein kinase 6 and a C-type lectin for male adults. These findings provide insight into the development and physiology of Culex mosquitoes, which will help in the development of more effective control methods for these disease vectors.

Comparative studies of stenogamous behaviour in the mosquito Culex pipiens complex.

Understanding the processes of reproductive behaviour in mosquitoes is crucial for improving mating competitiveness and mating specificity for sterile insect release programmes. The Culex pipiens (Linneaus) (Diptera: Culicidae) forms pipiens and molestus (Forskål), two biotypes of the Cx. pipiens complex, are vectors for West Nile virus, St Louis encephalitis virus and lymphatic filariases. Hybridization of these biotypes is known to occur in nature, although form pipiens mates above ground in large spaces (eurygamy) and form molestus preferentially mates in small spaces (stenogamy) such as sewage tunnels. Hybridization may allow gene flow of biotype-specific characteristics that are crucial in the disease transmission cycle. The present study examined and compared mating behaviours, insemination rates, fecundity and fertility in parental and F1 hybrids between Cx. pipiens f. pipiens and Cx. pipiens f. molestus in conditions of stenogamy. Unique mating behaviour sequences were identified in Cx. pipiens f. molestus, including tapping, mounting, co-flying and copulation. Despite the considerably high insemination rates in hybrid crosses, fertility and fecundity rates were varied. This observation could suggest reproductive isolation in the hybrid zone. The study also documents a failure of heterospecific males to produce fertile eggs in Cx. pipiens f. pipiens females, which may be attributable to gametic incompatibilities and may represent an additional barrier to gene exchange.

Pseudoepitheliomatous keratotic and micaceous balanitis treated with topical 5-fluorouracil and liquid nitrogen.

Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is an uncommon premalignant condition involving the glans penis. We report the case of an 86-year-old man who presented with phimosis and pain on retracting his foreskin. He had previously undergone circumcision, which revealed a hyperkeratotic plaque with thin mica-like scales involving his glans penis. Histology of the lesion showed hyperkeratosis, parakeratosis, epidermal acanthosis and papillomatosis with no evidence of dysplasia. Immunohistochemistry for human papillomavirus was negative. The patient was treated with topical 5-fluorouracil and liquid nitrogen with clinical improvement. He is now under long-term surveillance for verrucous carcinoma and squamous cell carcinoma.

Performance of a pilot showcase of different wetland systems in an urban setting in Singapore.

The Alexandra Wetlands, part of PUB's Active, Beautiful, Clean Waters (ABC Waters) Programme, showcase a surface flow wetland, an aquatic pond and a sub-surface flow wetland on a 200 m deck built over an urban drainage canal. Water from the canal is pumped to a sedimentation basin, before flowing in parallel to the three wetlands. Water quality monitoring was carried out monthly from April 2011 to December 2012. The order of removal efficiency is sub-surface flow (81.3%) >aquatic pond (58.5%) >surface flow (50.7%) for total suspended solids (TSS); sub-surface (44.9%) >surface flow (31.9%) >aquatic pond (22.0%) for total nitrogen (TN); and surface flow (56.7%) >aquatic pond (39.8%) >sub-surface flow (5.4%) for total phosphorus (TP). All three wetlands achieved the Singapore stormwater treatment objectives (STO) for TP removal, but only the sub-surface flow wetland met the STO for TSS, and none met the STO for TN. Challenges in achieving satisfactory performance include inconsistent feed water quality, undesirable behaviour such as fishing, release of pets and feeding of animals in the wetlands, and canal dredging during part of the monitoring period. As a pilot showcase, the Alexandra Wetlands provide useful lessons for implementing multi-objective wetlands in an urban setting.

Management and treatment of landfill leachate by a system of constructed wetlands and ponds in Singapore.

Lorong Halus, Singapore's first landfill leachate treatment system, consists of a pre-treatment system (8,000 m(2)), five constructed reed beds (38,000 m(2)), five polishing ponds (13,000 m(2)), an education centre and a learning trail for visitors. Eight species of wetland plants (total 160,000 plants) were selected for their ability to uptake nutrients, tolerance to low phosphorus concentrations and resistance to pest infestations. The wetland was launched in March 2011 and water quality monitoring started in April 2011. The removal efficiencies of the pre-treatment system from April 2011 to August 2012 are biochemical oxygen demand (BOD5) 57.4%; chemical oxygen demand (COD) 23.6%; total suspended solids (TSS) 55.1%; ammoniacal nitrogen (NH4-N) 76.8%; total phosphorus (TP) 33.3% and total nitrogen (TN) 60.2%. Removal efficiencies of the reed beds are BOD5 47.0%; COD 42.2%; TSS 57.0%; NH4-N 82.5%; TP 29.3% and TN 83.9%. Plant growth is generally satisfactory, but the lower than designed volume of leachate has adversely affected some sections of plants and resulted in uneven flow distribution in reed beds. The plant management programme includes improving plant regrowth by harvesting of alternate strips of plants and replanting. The treated effluent meets water quality limits for discharge to the public sewer and is subsequently treated by the NEWater treatment system, which recycles water for industrial and indirect potable use.

APSIC dental infection prevention and control (IPC) guidelines.

BACKGROUND: The Asia Pacific Society of Infection Control launched the Infection Prevention and Control Guidelines in July 2022. This document describes the guidelines and recommendations for safe practices in dental setting. It aims to highlight practical recommendations in a concise format designed to assist dental facilities at Asia Pacific region in achieving high standards in infection prevention and control practices, staff and patient safety. METHOD: The guidelines were developed by an appointed workgroup comprising experts in the Asia Pacific region, following reviews of previously published international guidelines and recommendations relevant to each section. RESULTS: It recommends standard precautions as a minimal set of preventive measures to protect staff and prevent cross transmission. Surgical aseptic technique is recommended when procedures are technically complex and longer in duration. Only trained staff are eligible to conduct reprocessing of dental instruments. The design, layout of the dental facility are important factors for successful infection prevention. The facility should also have a Pandemic Preparedness Plan. CONCLUSIONS: Dental facilities should aim for excellence in infection prevention and control practices as this is part of patient safety. The guidelines that come with a checklist help dental facilities to identify gaps for improvement to reach this goal.

Transcription profiling associated with life cycle of Anopheles gambiae.

Complex biological events occur during the developmental process of the mosquito Anopheles gambiae (Giles). Using cDNA expression microarrays, the expression patterns of 13,440 clones representing 8,664 unique transcripts were revealed from six different developmental stages: early larvae (late third instar/early fourth instar), late larvae (late fourth instar), early pupae (< 30 min after pupation), late pupae (after tanning), and adult female and male mosquitoes (24 h postemergence). After microarray analysis, 560 unique transcripts were identified to show at least a fourfold up- or down-regulation in at least one developmental stage. Based on the expression patterns, these gene products were clustered into 13 groups. In total, eight genes were analyzed by quantitative real-time polymerase chain reaction to validate microarray results. Among 560 unique transcripts, 446 contigs were assigned to respective genes from the An. gambiae genome. The expression patterns and annotations of the genes in the 13 groups are discussed in the context of development including metabolism, transport, protein synthesis and degradation, cellular processes, cellular communication, intra- or extra-cellular architecture maintenance, response to stress or immune-related defense, and spermatogenesis.

Rinsing with water for 1 min after milk formula increases plaque pH.

PURPOSE: Parents find it challenging to follow recommendations to brush young children after feeds at night despite the increase caries risk. This study compared three clinical recommendations (dilution, rinsing and wiping) on plaque pH after formula consumption. METHODS: Eighteen subjects were recruited. The five interventions with 2-week washout between visits included: Rinse with undiluted formula for 30 s (UF); rinse with 50% diluted formula for 30 s (DF); rinse with undiluted formula for 30 s, followed by rinsing with water for 1 minute (UF/R); rinse with undiluted formula for 30 s, followed by wiping (UF/W); rinse with 10% sucrose for 30 s as control (C). Plaque samples were collected at baseline, 2, 5, 10, 20 and 30 min after the intervention and pH measured using the plaque sampling method. RESULTS: UF/R resulted in significantly smaller pH drops at 5, 10 and 20 min compared to UF. It also resulted in higher minimum pH (UF/R: 6.34 ± 0.36 Vs UF: 6.06 ± 0.40, p = 0.02), smaller maximum pH drop (UF/R: 0.63 ± 0.35 Vs UF: 0.90 ± 0.49, p = 0.03), smaller sum of change of hydrogen ion concentration (UF/R: 9.22 × 10-7 ± 7.8 × 10-7 Vs UF: 2.30 × 10-6 ± 2.6 × 10-6, p = 0.04), and smaller area under the curve (UF/R: 7.70 ± 5.44 Vs UF: 13.44 ± 9.44, p = 0.02). DF and UF/W did not result in any significant pH change compared to UF. CONCLUSIONS: Of the three clinical recommendations, only rinsing with water for 1 min after undiluted formula reduced plaque acidogenicity. Teeth wiping with a moist cloth and 50% dilution of infant formula did not have an effect on plaque acidity.

Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease.

Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.

RNA interference directed against ribosomal protein S3a suggests a link between this gene and arrested ovarian development during adult diapause in Culex pipiens.

Arrested ovarian development is a key characteristic of adult diapause in the mosquito Culex pipiens. In this study we propose that ribosomal protein S3a (rpS3a), a small ribosomal subunit, contributes to this shutdown. RpS3a is consistently expressed in females of C. pipiens that do not enter diapause, but in females programmed for diapause, expression of the rpS3a transcript is dramatically reduced for a brief period in early diapause (7-10 days after adult eclosion). RNA interference directed against rpS3a in nondiapausing females arrested follicle development, mimicking the diapause state. The effect of the dsRNA injection faded within 10 days, allowing the follicles to grow again, thus the suppression of rpS3a caused by RNAi did not permanently block ovarian development, implying that a brief suppression of rpS3a is not the only factor contributing to the diapause response. The arrest in development that we observed in dsRNA-injected females could be reversed with a topical application of juvenile hormone III, an endocrine trigger known to terminate diapause in this species. Though we speculate that many genes contribute to the diapause syndrome in C. pipiens, our results suggest that a shut down in the expression of rpS3a is one of the important components of this developmental response.

A randomized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease.

OBJECTIVES: The safety and efficacy of early acetylcholinesterase inhibitors therapy in patients with cognitive impairment no dementia (CIND) after a cerebrovascular accident have not been examined. In this study, we investigated the safety and efficacy of rivastigmine in cognition, particularly executive function in patients with CIND because of cerebrovascular disease. METHODS: This study was a 24-week, double-blind, randomized, placebo-controlled trial of ischemic stroke patients seen at a tertiary hospital who had cognitive impairment no dementia because of cerebrovascular disease. The intervention was either rivastigmine or placebo up to 9 mg/day. The primary outcome of interest was mean change from baseline in the Ten-Point Clock Drawing and Color Trails 1 and 2. RESULTS: Fifty patients were randomized into rivastigmine (n = 25) and placebo (n = 25) arms. Patients in the rivastigmine group showed statistically significant improvement (1.70 vs 0.13, P = 0.02) on the animal subtask of the verbal fluency measure compared with placebo. There was also a trend (non-significant) towards improvement in Color Trails II. CONCLUSIONS: In this pilot study, we demonstrated that rivastigmine was well tolerated in patients with CIND because of cerebrovascular disease and may potentially improve executive functioning.

Over-expression of cyclo-oxygenase-2 predicts poor survival of patients with nasopharyngeal carcinoma: a meta-analysis.

OBJECTIVES: The conclusive prognostic significance of cyclo-oxygenase-2 has been determined in various cancers but not in nasopharyngeal carcinoma. Therefore, this study aimed to evaluate the relationship of cyclo-oxygenase-2 expression with the survival outcome and treatment response of nasopharyngeal carcinoma patients via a systematic meta-analysis approach. METHODS: A meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses ('PRISMA') checklist. The primary clinical characteristics of patients, and hazard ratios with 95 per cent confidence intervals of overall survival data, were tabulated from eligible studies. The relationship of cyclo-oxygenase-2 expression with survival outcome (expressed as hazard ratio) and treatment response (expressed as odds ratio) in nasopharyngeal carcinoma patients was analysed, and explained with the aid of forest plot charts. RESULTS AND CONCLUSION: The pooled hazard ratio for overall survival was 2.02 (95 per cent confidence interval = 1.65-2.47). This indicates that the over-expression of cyclo-oxygenase-2 is significantly associated with the poor survival of nasopharyngeal carcinoma patients. The pooled odds ratio of 0.98 (95 per cent confidence interval = 0.27-3.49) reveals that over-expression of cyclo-oxygenase-2 was not significantly related to the treatment outcome.

A shut-down in expression of an insulin-like peptide, ILP-1, halts ovarian maturation during the overwintering diapause of the mosquito Culex pipiens.

Short day-length is used to programme adult diapause in the mosquito, Culex pipiens. The downstream endocrine event that halts ovarian maturation is a shut-down in juvenile hormone (JH) production, and recent evidence suggests that the insulin signalling pathway may be a key upstream player in executing this developmental arrest. Genes encoding insulin-like peptides-1, -2 and -5 were identified in C. pipiens, and we report that transcript levels of insulin-like peptides-1 and -5 were significantly lower in diapausing females than in their nondiapausing counterparts. Genes encoding both insulin-like peptides-1 and -5 were suppressed using RNA interference in mosquitoes programmed for nondiapause, and ovarian maturation was monitored. Knocking down insulin-like peptide-1 with RNAi in nondiapausing mosquitoes resulted in a cessation of ovarian development akin to diapause, and this arrest in development could be reversed with an application of JH. Knocking down insulin-like peptide-5 did not alter ovarian development. These results are consistent with a role for insulin-like peptide-1 in the signalling pathway leading from the perception of short day-lengths to the shut-down in JH production that characterizes adult diapause in C. pipiens.

CPP-ACP Promotes SnF2 Efficacy in a Polymicrobial Caries Model.

Dental caries is associated with plaque dysbiosis, leading to an increase in the proportions of acidogenic and aciduric bacteria at the expense of alkali-generating commensal species. Stannous fluoride (SnF2) slows the progression of caries by remineralization of early lesions but has also been suggested to inhibit glycolysis of aciduric bacteria. Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) promotes fluoride remineralization by acting as a salivary biomimetic that releases bioavailable calcium and phosphate ions, and the peptide complex has also been suggested to modify plaque composition. We developed a polymicrobial biofilm model of caries using 6 bacterial species representative of supragingival plaque that were cultured on sound human enamel and pulsed with sucrose 4 times a day to produce a high cariogenic challenge. We used this model to explore the mechanisms of action of SnF2 and CPP-ACP. Bacterial species in the biofilms were enumerated with 16S rRNA gene sequence analyses, and mineral loss and lesion formation were determined in the enamel directly under the polymicrobial biofilms via transverse microradiography. The model tested the twice-daily addition of SnF2, CPP-ACP, or both. SnF2 treatment reduced demineralization by 50% and had a slight effect on the composition of the polymicrobial biofilm. CPP-ACP treatment caused a similar inhibition of enamel demineralization (50%), a decrease in Actinomyces naeslundii and Lactobacillus casei abundance, and an increase in Streptococcus sanguinis and Fusobacterium nucleatum abundance in the polymicrobial biofilm. A combination of SnF2 and CPP-ACP resulted in a greater suppression of the acidogenic and aciduric bacteria and a significant 72% inhibition of enamel demineralization.

Mutational Signatures in Mandibular Ameloblastoma Correlate with Smoking.

Ameloblastoma is a rare tumor of odontogenic epithelium, the low incidence rate of which precludes statistical determination of its molecular characterizations. Despite recent genomic and transcriptomic profiling, the etiology of ameloblastomas remains poorly understood. Risk factors of ameloblastoma development are also largely unknown. Whole exome sequencing was performed on 11 mandibular ameloblastoma samples. We identified 2 convergent mutational signatures in ameloblastoma: 1) a signature found in multiple types of lung cancers with probable etiology of tobacco carcinogens (COSMIC signature 4) and 2) a signature present in gingivobuccal oral squamous cell carcinoma and correlated with tobacco-chewing habits (COSMIC signature 29). These mutational signatures highlight tobacco usage or related mutagens as one possible risk factor of ameloblastoma, since the association of BRAF mutations and smoking was demonstrated in multiple studies. In addition to BRAF hotspot mutations (V600E), we observed clear inter- and intratumor heterogeneities. Interestingly, prior to BRAF mutation, important genes regulating odontogenesis mutated (e.g., corepressor BCOR), possibly playing important roles in tumorigenesis. Furthermore, recurrent mutations in the CDC73 gene, the germline mutations of which predispose patients to the development of jaw tumors, were found in 2 patients, which may lead to recurrence if not targeted by therapeutic drugs. Our unbiased profiling of coding regions of ameloblastoma genomes provides insights to the possible etiology of mandibular ameloblastoma and highlights potential disease risk factors for screening and prevention, especially for Asian patients. Because of the limited sample size and incomplete habitual, dietary, and occupational data, a causal link between tobacco usage and ameloblastoma still requires further investigations.

Donor MHC and adhesion molecules in transplant arteriosclerosis.

Transplant-associated arteriosclerosis remains an obstacle to long-term graft survival. To determine the contribution to transplant arteriosclerosis of MHC and adhesion molecules from cells of the donor vasculature, we allografted carotid artery loops from six mutant mouse strains into immunocompetent CBA/CaJ recipients. The donor mice were deficient in either MHC I molecules or MHC II molecules, both MHC I and MHC II molecules, the adhesion molecule P-selectin, intercellular adhesion molecule (ICAM)-1, or both P-selectin and ICAM-1. Donor arteries in which ICAM-1, MHC II, or both MHC I and MHC II were absent showed reductions in neointima formation of 52%, 33%, and 38%, respectively, due primarily to a reduction in smooth muscle cell (SMC) accumulation. In P-selectin-deficient donor arteries, neointima formation did not differ from that in controls. In donor arteries lacking both P-selectin and ICAM-1, the size of the neointima was similar to that in those lacking ICAM-1 alone. In contrast, neointima formation increased by 52% in MHC I-deficient donor arteries. The number of CD4-positive T cells increased by 2.8-fold in MHC I-deficient arteries, and that of alpha-actin-positive SMCs by twofold. These observations indicate that ICAM-1 and MHC II molecules expressed in the donor vessel wall may promote transplant-associated arteriosclerosis. MHC I molecules expressed in the donor may have a protective effect.

Manganese does not alter the severe neurotoxicity of MPTP.

We utilized a mice model of Parkinsonism: (1) to evaluate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity; and (2) to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. A 2 x 3 experimental design (MPTP x+/- Mn) was as follows: SS, MPTP(-) x Mn(-); SLMn, MPTP(-) x low Mn(+); SHMn, MPTP(-) x high Mn(+); MpS, MPTP(+) x Mn(-); MpLMn, MPTP(+) x low Mn(+); MpHMn, MPTP(+) x high Mn(+). We administered MPTP (30 mg/kg per day) to male C57BL/6 mice intraperitoneally, once a day for 5 days. Subsequently, mice were treated with either 2 or 8 mg/kg of MnCl(2).4H(2)O intraperitoneally, once a day for 3 weeks. Blood and striatal Mn levels were elevated in the Mnexposed groups. The number of tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta were decreased significantly in the MPTP-exposed groups. The densities of TH-ir axon terminals in caudate-putamen (CPU) were significantly decreased in the MPTP-treated groups. However, Mn treatment did not affect MPTP neurotoxicity. The densities of glial fibrillary acidic protein (GFAP)-ir astrocytes in the CPU or globus pallidus were significantly increased in the MPTP-treated groups. Concentrations of dopamine in the striatum were decreased significantly in the MPTP-exposed groups only, but Mn had no effect.

The effectiveness of exercise programmes in patients with multiple myeloma: A literature review.

A limited number of clinical studies have investigated the effectiveness of participation in exercise training programmes for patients with multiple myeloma (MM), exploring the different biomedical, physical, psychological and quality of life. The aim of this literature review is to evaluate current quantitative and qualitative evidence concerning the effectiveness of participation in exercise programmes for patients with MM in improving physiological and/or psychological status. A literature search encompassing studies published between January 1998 and July 2013 was conducted through ten electronic databases. This search was further expanded through citation chaining, manual grey literature searches, and peer review consultation. In total, seven interventional studies were identified and appraised using Critical Appraisal Skill Programme (CASP) or Centre for Evidence-Based Management of Amsterdam (CEBMa). Though the majority of the studies presented encouraging data, however, three studies that implemented individualized exercise interventions for patients at different stages of MM and myeloablative treatment showed mixed results. In conclusion, the effectiveness of participation in exercise programmes remains unclear for patients with MM, as the studies reviewed were flawed by relatively weak methodological approaches.

Endotoxin-induced mortality is related to increased oxidative stress and end-organ dysfunction, not refractory hypotension, in heme oxygenase-1-deficient mice.

BACKGROUND: Heme oxygenase (HO)-1 is an enzyme that degrades heme to generate CO (a vasodilatory gas), iron, and the potent antioxidant bilirubin. A disease process characterized by decreases in vascular tone and increases in oxidative stress is endotoxic shock. Moreover, HO-1 is markedly induced in multiple organs after the administration of endotoxin (lipopolysaccharide [LPS]) to mice. METHODS AND RESULTS: To determine the role of HO-1 in endotoxemia, we administered LPS to mice that were wild-type (+/+), heterozygous (+/-), or homozygous null (-/-) for targeted disruption of HO-1. LPS produced a similar induction of HO-1 mRNA and protein in HO-1(+/+) and HO-1(+/-) mice, whereas HO-1(-/-) mice showed no HO-1 expression. Four hours after LPS, systolic blood pressure (SBP) decreased in all the groups. However, SBP was significantly higher in HO-1(-/-) mice (121+/-5 mm Hg) after 24 hours, compared with HO-1(+/+) (96+/-7 mm Hg) and HO-1(+/-) (89+/-13 mm Hg) mice. A sustained increase in endothelin-1 contributed to this SBP response. Even though SBP was higher, mortality was increased in HO-1(-/-) mice, and they exhibited hepatic and renal dysfunction that was not present in HO-1(+/+) and HO-1(+/-) mice. The end-organ damage and death in HO-1(-/-) mice was related to increased oxidative stress. CONCLUSIONS: These data suggest that the increased mortality during endotoxemia in HO-1(-/-) mice is related to increased oxidative stress and end-organ (renal and hepatic) damage, not to refractory hypotension.

Twelve-nucleotide repeat polymorphism of D4 dopamine receptor gene in Chinese familial schizophrenic patients.

BACKGROUND: Disturbances in dopaminergic transmission have been implicated in the etiology of schizophrenia. Catalano et al reported an association between delusional disorder and the number of a 12-nucleotide (bp) repeat sequence in the first exon of dopamine D4 receptor gene (DRD4), which indicated a possible role of this polymorphism in the pathogenesis of psychotic disorders. METHODS: DNA of 42 Chinese controls, 50 sporadic schizophrenic patients, and 30 familial schizophrenic probands were collected. Genotype of the 12-bp repeat polymorphism of DRD4 was determined with polymerase chain reaction and agarose gel electrophoresis. Genotypic and allelic frequencies were compared among the three groups using the chi-square test. RESULTS: Forty-three (86%) sporadic schizophrenic patients, 25 (83.3%) familial schizophrenic probands, and 35 (83.3%) controls were A1 (two 12-bp repeat) homozygotes. One (2.0%) sporadic schizophrenic and 1 familial schizophrenic patient were A2 (one 12-bp repeat) homozygotes. There was no significant difference in allelic and genotypic distributions among the three groups. CONCLUSIONS: The present data do not support an association between schizophrenia and any specific allele of the 12-bp repeat polymorphism of DRD4. Significance of familial/sporadic division of schizophrenia cannot be supported regarding this repeat polymorphism.