TNFSF14 mediates the impact of docosahexaenoic acid on atopic dermatitis: a Mendelian randomization study.

OBJECTIVE: While current research suggests potential value for docosahexaenoic acid (DHA) in the prevention and management of atopic dermatitis (AD), the causal relationship between DHA and AD remains unclear, and the underlying mechanisms are not well understood. MATERIALS AND METHODS: To investigate the potential causal relationship between DHA and AD, as well as to explore potential mediating mechanisms, we employed the Mendelian randomization (MR) methods. To study these potential relationships, we conducted MR analysis using publicly available Genome-Wide Association Studies (GWAS) data. Effect estimates were computed using the random-effects inverse-variance weighted method. RESULTS: Our study demonstrates a negative correlation between DHA levels and AD risk (OR: 0.915, 95% CI: 0.858-0.975, p=0.007). Furthermore, in MR analysis using tumor necrosis factor ligand superfamily member 14 (TNFSF14) levels as an outcome, DHA levels also show a negative association with TNFSF14 levels (OR: 0.933, 95% CI: 0.879-0.990, p=0.022). Subsequently, we performed further analysis to explore the relationship between TNFSF14 and AD risk, revealing a positive correlation (OR: 1.069, 95% CI: 1.005-1.137, p=0.033). This suggests a potential mediating role of TNFSF14 in the impact of DHA on AD risk. CONCLUSIONS: In summary, our study employs MR analysis to offer genetic evidence indicating a potential role of DHA in reducing the risk of AD, as well as opening avenues for further in-depth investigation into potential mechanisms. These findings emphasize the importance of ongoing research in this field.

A long non-coding RNA, ELFN1-AS1, sponges miR-1250 to upregulate MTA1 to promote cell proliferation, migration and invasion, and induce apoptosis in colorectal cancer.

OBJECTIVE: Long non-coding RNA (lncRNA), is essential for the development and progression of cancers. LncRNA regulates target gene expression by sponging the corresponding microRNA (miRNA) during tumorigenesis. This work aimed to explore the role of one lncRNA, ELFN1-AS1, in colorectal cancer (CRC) development and elucidate the pertinent signaling pathway. PATIENTS AND METHODS: First, we found that ELFN1-AS1 was highly abundant in the human CRC tissues and cell lines. Silence of ELFN1-AS1 expression reduced cell proliferation, colony formation, migration and invasion, while inducing apoptosis in vitro; moreover, knockdown of ELFN1-AS1 decreased the size and weight of tumor in vivo. RESULTS: Luciferase reporter assay revealed that ELFN1-AS1 interacted with miR-1205 and suppressed its expression. In addition, miR-1205 could bind to the 3' untranslated region (3'-UTR) of Metastasis Associated Protein1 (MTA1) and inhibited ELFN1-AS1 expression. More importantly, overexpression of MTA1 completely rescued the phenotype of ELFN1-AS1 knockdown. CONCLUSIONS: In sum, our study demonstrated that ELFN1-AS1 sponges miR-1205 to upregulate MTA1, which is essential for CRC cell proliferation, migration, and invasion as well as apoptosis induction.

A NOVEL INTRAGENIC DELETION RELATED TO THE ARGININE VASOPRESSIN V2 RECEPTOR CAUSES NEPHROGENIC DIABETES INSIPIDUS.

BACKGROUND: Nephrogenic diabetes insipidus (NDI) is a disease characterized by a defective response to the antidiuretic hormone (ADH) of the renal collecting duct leading to a decline in the ability of the pro-urine concentration. CASE PRESENTATION: A 23-year-old man presented with an over 20-year history of polyuria concomitant with hydronephrosis. The diagnosis of NDI was established by gene analysis as well as a water-deprivation and vasopressin test. All exons of arginine vasopressin V2 receptor (AVPR2) gene were amplified and sequenced. A novel hemizygous intragenic inframe deletion, cDNA 255th bp to 263th bp in exon 2 of AVPR2, was identified. These relevant translations from the 85th amino acid Asp to 88th amino acid Val were missed and replaced by amino acid Glu. After treating the patient with hydrochlorothiazide, his symptoms improved significantly. CONCLUSION: The genetic analysis revealed a novel X-linked intragenic inframe deletion, AVPR2 gene cDNA 255th bp to 263th bp, causing NDI.

BIOINFORMATIC ANALYSIS IDENTIFIES POTENTIALLY KEY DIFFERENTIALLY EXPRESSED GENES AND PATHWAYS IN ORBITAL ADIPOSE TISSUES OF PATIENTS WITH THYROID EYE DISEASE.

CONTEXT: Thyroid eye disease (TED), an orbital inflammatory status, generally occurred in Graves' disease. OBJECTIVE: This study aimed to acquire further insight into molecular mechanisms of TED, especially several key involved genes and pathways. DESIGN: The microarray dataset GSE58331 including expression data for orbital adipose tissue samples, isolated from TED patients and normal controls, was downloaded from a publicly accessible Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified from 23 adipose tissues of TED patients versus 20 samples from normal controls. SUBJECTS AND METHODS: A protein-protein interaction network of DEGs was constructed by using Search Tool for the Retrieval of Interacting Genes and Cytoscape 3.6.0. Several hub genes/proteins were extracted from the protein-protein interaction network based on connectivity degree. Furthermore, we used the iRegulon plugin of Cytoscape3.6.0 to predict the transcription factors (TFs). RESULTS: A total of 678 DEGs (538 up- and 140 down-regulated genes) were identified in TED patients. Proopiomelanocortin (POMC), interleukin 2 (IL-2), G protein subunit gamma 3 (GNG3), CXC motif chemokine receptor 4 (CXCR4), toll like receptor 4 (TLR4), colony stimulating factor 1 receptor (CSF1R), lysophosphatidic acid receptor 3 (LPAR3), CXC motif chemokine ligand-8 (CXCL8), etc., were considered as the hub genes among the DEGs. There were 6 TFs predicted to be differentially expressed in regulating the DEGs related to TED. A total of 71 DEGs had been reported to be associated with TED in the Comparative Toxicogenomics Database. CONCLUSIONS: Through this analysis, we have identified plenty of potential biomarkers and pathways which may have an important role in the pathogenesis of TED. However, these findings require verification by more detailed future experimental studies.

Effects of microRNAs on skeletal muscle development.

MicroRNAs (miRNAs) are small (about 22 nucleotides) noncoding RNAs, which were highly conserved among mammals. They have ushered in a new era in molecular biology over twenty years. They can negatively regulate gene expression at the posttranscriptional level through the principle of complementary base pairing with the 3' untranslated region (UTR) of their target mRNAs and induce their degradation. They involve in tissue morphogenesis, cellular processes like apoptosis, and major signaling pathways. Previous studies have promoted our understanding that miRNAs play an important role in myogenesis and have a big impact on muscle mass, muscle fiber type and muscle diseases. Many researchers have provided evidence of the involvement of muscle-specific and enriched miRNAs in the individual stages of skeletal muscle development as well as of their significant influence on muscle metabolism during quiescence, proliferation, differentiation and regeneration. Here, we focus on the microRNAs that related to the development of skeletal muscle. For example, some microRNAs are upregulated in differentiated skeletal muscle and can promote differentiation, like, miR-1, miR-24, miR-26a, miR-181 and miR-206. However, some microRNAs highly expressed in proliferating myoblasts, downregulated in differentiated and could inhibit differentiation, like MiR-221 and miR-222. Some others not only promote skeletal muscle proliferation, but also promote differentiation, like miR-214. Studying the miRNAs' regulatory mechanisms in skeletal development will help us know more about the knowledge of miRNAs in muscle developmental biology and make us learn more about involved signal pathway.

HEMOGLOBIN A1c LEVEL HIGHER THAN 9.05% CAUSES A SIGNIFICANT IMPAIRMENT OF ERYTHROCYTE DEFORMABILITY IN DIABETES MELLITUS.

CONTEXT: Clinical studies demonstrated erythrocyte deformability (ED) is impaired in diabetic patients and described the correlations between HbA1c and ED. Few studies further investigated what an exact elevated HbA1c level linked to the impairment of ED in diabetes. OBJECTIVE: This study was to determine a cut-off point of HbA1c level leading to the impairment of ED in patients with diabetes. DESIGN: This was a retrospective observational study. ROC curve analysis was used to determine an optimal cut-off value of HbA1c for the increasing HSRV. SUBJECTS AND METHODS: In this study, 300 type 2 diabetic patients were enrolled. The whole blood viscosity was measured. High shear reductive viscosity (HSRV) was used to indirectly estimate ED. Based on the obtained cut-off value and glycemic control criteria for HbA1c, we divided all the cases into different groups to further confirm the accuracy of the cut-off value. RESULTS: In 300 patients, ROC curve illustrated that 9.05% was the optimal cut-off value as a predictor of the increasing HSRV. And higher odds ratio (OR) for significant decrease in ED was seen in the patients with HbA1c >9.05% compared to those with HbA1c≤9.05% (OR: 3.78, 95% CI: 2.08-6.87). HSRV increased significantly in patients with HbA1c level >9.05% in comparison to patients with HbA1c levels <6.5% between 6.5 and 8.0% and between 8.0 and 9.05%. CONCLUSION: ED decreased significantly in diabetic patients as soon as HbA1c level was higher than 9.05%.

Ultrastructural and Cytochemical Properties of Peripheral Blood Cells of Piebald Naked Carp (Gymnocypris eckloni).

The ultrastructural and cytochemical properties of peripheral blood cells of Gymnocypris eckloni were investigated by transmission electron microscopy and a range of cytochemical techniques to provide clear insight into the structure and function of blood cells from this fish. Ultrastructurally, erythrocytes, leucocytes (neutrophils, eosinophils, lymphocytes, monocytes), thrombocytes and plasma cells were identified in the peripheral blood of G. eckloni. The most special ultrastructural characteristics of blood cells in this fish were that neutrophils exhibited only one type of cytoplasmic granules containing an eccentric, spherical or oval electron-dense core, and eosinophils presented two types of granules with non-uniform electronic density and without crystalloids in their cytoplasm. Neutrophils, eosinophils, lymphocytes, monocytes and thrombocytes were positive for periodic acid-Schiff and α-naphthyl acetate esterase staining. Intense peroxidase positive staining was observed in neutrophils and monocytes, but not in eosinophils, lymphocytes and thrombocytes. Neutrophils, eosinophils and monocytes were stained positively for acid phosphatase, whereas lymphocytes and thrombocytes did not stain. Leucocytes and thrombocytes were negative for alkaline phosphatase and Sudan black B staining. Erythrocytes were negative for all cytochemical staining. The cytochemical and ultrastructural features of peripheral blood cells of G. eckloni were similar to those of other fish species. However, some important differences were identified in G. eckloni.

[Effects and clinical significance of virus load on red blood cell parameters in different stage of hepatitis B].

OBJECTIVE: To evaluate the effect of the viral load on the red blood cell parameters in chronic hepatitis B patients and its clinical significance. METHODS: In the study, 373 chronic hepatitis B patients were recruited, including 123 alanine transaminase (ALT) normal patients (ALT<40 U/L),128 ALT greater than or equal to the upper limit of normal, and less than 2 times higher than the upper limit of normal patients(40 U/L ≤ALT<80 U/L), and 122 ALT greater than or equal to 2 times higher than the upper limit of normal patients (ALT≥80 U/L). The blood routine parameters were measured by automatic blood cell counter. The liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus loads were measured by quantitative PCR analyzer and the results were analyzed by covariance analysis. RESULTS: In the ALT normal chronic hepatitis B patients group, the viral load had minor effects on the red blood cell parameters.But in the ALT abnormal chronic hepatitis B patients group, the viral load had a significant effect on the red blood cell parameters, and the effect was most manifest in the ALT≥ double upper limit of normal group. The specific performance was that with the viral load increasing, the red blood cell [low copies group (4.10±0.67)×10(12)/L,medium copies group (3.92±0.69)×10(12)/L,high copies group (3.54±0.90) ×10(12)/L], the hemoglobin[low copies group (129.66±21.12 ) g/L, medium copies group (126.23±23.38) g/L, high copies group (112.98±27.77) g/L], the hematocrit (low copies group 37.66±5.68, medium copies group 37.03±6.03, high copies group 33.34±8.15) decreased(P=0.006,0.007,0.010),the mean corpuscular volume [low copies group (92.17±6.53) fL, medium copies group (94.85±7.95) fL, high copies group (101.63±11.33) fL], the mean corpuscular hemoglobin [low copies group (31.70±2.22) pg, medium copies group (33.11±3.62) pg, high copies group (34.65±3.13) pg], the mean corpuscular hemoglobin concentration [low copies group (344.28±17.17) g/L, medium copies group (351.33±16.90) g/L, high copies group (358.12±15.67) g/L], and the red blood cell distribution width-standard deviation [low copies group (52.49±9.04) fL, medium copies group (56.96±7.19) fL, high copies group (61.23 ±7.23) fL] increased(P=0.000,0.000,0.002,0.000). CONCLUSION: Observing the effect of the viral load on the red blood cell parameters in chronic hepatitis B patients can reflect the effect of hepatitis B virus on the immune response and liver function in the different pathological stages, providing theoretical support for the clinical antiviral treatment.

Rosiglitazone protects diabetic rats from liver destruction.

AIMS: To investigate whether rosiglitazone (ROS) protects diabetic rats from destructive changes in the liver. METHODS: Twenty-four Sprague Dawley rats were randomly divided into 3 groups: control (NC) group (no.=8), streptozocin (STZ)-treated diabetic (DM) group (no.=8), and STZ+ROStreated diabetic (RSG) group (no.=8). After 8 weeks, the liver structure was observed by light microscopy and transmission electron microscopy. Apoptosis was detected by TUNEL, and apoptosis index was calculated. The Fas ligand (FasL) mRNA expression of apoptosis-promoting gene and cyclooxygenase- 2 (COX-2) mRNA in the liver were detected by RTPCR. COX-2 protein in the liver was tested via immunohistochemical staining. RESULTS: Compared to NC group, DM group showed a visible fatty degeneration and inflammatory cell infiltration in the liver under microscopy. Obvious hepatocyte swelling with atrophic mitochondria was observed, and the central zone of cholangiole was severely outstretched. Meanwhile, in RSG group, the hepatocyte steatosis and inflammatory cell infiltration decreased, and the hepatic ultra-structure was markedly improved. Hepatocyte apoptosis (p<0.05) and the expression levels for hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), and COX-2 protein (p<0.05) were higher in DM group compared to the NC group, while the expression level of hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), COX-2 protein (p<0.05), and hepatocyte apoptosis (p<0.05) in RSG group were decreased compared to DM group. CONCLUSION: Diabetes causes severe liver injury and ROS can protect diabetic rats from liver destruction, which may be related to inhibition of the expression of COX-2 and the hepatocyte apoptosis induced by FasL gene over expression.

Mitochondrial apoptotic pathways: a mechanism for low androgen-induced vascular endothelial injury in male rats.

The aim of the study was to investigate the role of mitochondrial apoptotic pathways in vascular endothelial injury in male rats with low androgen. 8 week-old adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups (n=6/each group): control group, castrated group (low androgen), and replacement group (given androgen after castration). After 10 weeks, endothelial structure was observed by general light microscope and transmission electron microscope (TEM) respectively. Isolated mitochondria and mitochondrial membrane potential (MMP) were detected by fluorescence to access mitochondrial function. Chromatin degradation was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick end labeling (TUNEL) staining method. The mRNA and protein of bcl-2, cytochrome C (Cyt C), caspase-9, and caspase-3 were analyzed for apoptosis. Cell shrinkage and condensed chromatin, less mitochondria and a fall in MMP levels were observed in the castrated group, along with more apoptotic endothelial cells. Bcl-2 level was reduced and the expression of caspase-9, caspase-3 and Cyt C were elevated in the castrated group (p<0.05). But there was no significant difference between the replacement group and the control group (p>0.05). It was concluded that low androgen caused vascular endothelial damage. It may be, at least in part, related with the activating mitochondrial apoptotic pathways.

Changes of pituitary and penile structure in male adult rats following castration and high-fat diet.

AIM: To investigate the influence of low androgen levels and high-fat diet on the structure of pituitary and penis in male rats. METHODS: Ten-week-old adult male Sprague-Dawley rats were randomly divided into 2 groups, one fed a high-fat diet the other fed a normal diet; each group consisted of 3 subgroups: controls, castrated rats (with low androgen), and castrated rats given undecanoate replenishment. After 11 weeks, the structure of pituitary and penis were observed under light microscopy. Immunohistochemistry was used to assess the expression of FSH in pituitary and cyclooxygenase-2 (COX-2) in corpora cavernosa penis. RESULTS: The structures of pituitary and penis in castrated rats were injured, and were more damaged in castration together with high-fat diet. Immunohistochemistry showed FSH expression in castrated rats pituitary while castrated rats on a high-fat diet had less positive staining than those on a normal diet. Vascular structure of corpora cavernosa penis, showed a strongly positive COX-2 expression in high-fat diet rats. CONCLUSIONS: Castration and high-fat diet could induce structural damages of pituitary and penis in male rats. Replacement with testosterone could partially restore the impaired structure. The positive expression of COX-2 implied inflammatory pathway existence on vascular structure of penis in high-fat diet and low-androgen male rats.

Effect of inhibition of the central nucleus of the amygdala and drug experience on the regions underlying footshock-induced reinstatement of morphine seeking.

This study assessed the effect of inhibition of the central nucleus of the amygdala (CeA) and drug experience on brain regions underlying footshock-induced reinstatement of morphine-seeking behaviour in rats. The difference in time spent in two chambers of a place preference apparatus was used to measure morphine-conditioned place preference. Fos was measured as a marker of neuronal activation in the ventral bed nucleus of the stria terminalis (BNSTv) and ventral tegmental area (VTA). Footshock was found to enhance Fos expression in the BNSTv regardless of drug experience. In the VTA, morphine and footshock had an interactive effect on the increase in Fos expression. Inhibition of the CeA decreased Fos expression in the BNSTv regardless of drug experience, whereas in the VTA this effect only occurred in morphine-treated rats. These results suggest that drug experience has no differential effect on the BNSTv however morphine produces footshock sensitization in the VTA. CeA inhibition modulates the footshock-induced activity of these regions of the brain and attenuates reinstatement of drug seeking behaviour.

Modeling fire-induced smoke spread and carbon monoxide transportation in a long channel: Fire Dynamics Simulator comparisons with measured data.

Smoke and toxic gases, such as carbon monoxide, are the most fatal factors in fires. This paper models fire-induced smoke spread and carbon monoxide transportation in an 88m long channel by Fire Dynamics Simulator (FDS) with large eddy simulation (LES). FDS is now a well-founded fire dynamics computational fluid dynamic (CFD) program, which was developed by National Institute of Standards and Technology (NIST). Two full scale experiments with fire sizes of 0.75 and 1.6MW were conducted in this channel to validate the program. The spread of the fire-induced smoke flow together with the smoke temperature distribution along the channel, and the carbon monoxide concentration at an assigned position were measured. The FDS simulation results were compared with experimental data with fairly good agreement demonstrated. The validation work is then extended to numerically study the carbon monoxide concentration distribution, both vertically and longitudinally, in this long channel. Results showed that carbon monoxide concentration increase linearly with the height above the floor and decreases exponentially with the distance away from the fire source.

Ancient paddy soils from the Neolithic age in China's Yangtze River Delta.

Identifying prehistoric irrigated rice fields and characterizing the beginning of paddy soil development are important for a better understanding of human development and agricultural history. In 2003, paddy soils and irrigated rice fields buried at a depth of 100-130 cm were excavated at Chuo-dun-shan in the Yangtze River Delta, close to Suzhou, China. The fields of sizes between 1.4 and 16 m(2) were surrounded with ridges that were connected to ditches/ponds via outlets to control the water level within the fields. Many carbonized and partly carbonized rice grains with an age of 3,903 B.C. (measured (14)C age 5,129+/-45 a BP) were recovered. The surface layers of these buried paddy fields showed a high content of soil organic matter and a considerable high density of rice opals. The latter were identified to derive from Oryza spp. Solid-state (13)C nuclear magnetic resonance spectroscopy revealed aromatic carbon (C) as the predominant organic C form in the fossil surface layer. This is expected, if the major source represents burnt rice and straw. In summary, our data are in agreement with new evidences indicating that in China, paddy soils and irrigated rice cultivation were initiated and developed more than 6,000 years ago.

Nitrogen and phosphorus cycling in shrimp ponds and the measures for sustainable management.

Six ponds of age 3 were selected 45 km north from Suzhou in the Tailake region, and research conducted on nitrogen and phosphorus cycling in P. vannanmei (Penaeus vannanme) ponds and M. nipponense (Macrobrachium nipponense) hatchery ponds under normal management. Two treatments each had three replications. The results confirmed that feed was the major path of nitrogen and phosphorus input, each accounted for 61.24% (193.81 kg ha(-1)) and 81.08% (45.20 kg ha(-1)) of the total nitrogen and phosphorus input for P. vannanme ponds; the values for M. nipponense ponds were 43.93% (86.31 kg ha(-1)) and 57.67% (14.61 kg ha(-1)), respectively. Water pumped into ponds contributed on average 83.57 kg ha(-1) nitrogen and 8.48 kg ha(-1) phosphorus for P. vannanmei ponds, and 87.48 kg ha(-1) nitrogen and 7.00 kg ha(-1) phosphorus for M. nipponense hatchery ponds. Shrimp harvest recovered 102.81 kg ha(-1) nitrogen (32.94% of the total nitrogen input) and 7.94 kg ha(-1) phosphorus (14.23% of the total phosphorus input) for P. vannanme ponds; and 43.94 kg ha(-1) nitrogen and 4.46 kg ha(-1) phosphorus for M. nipponense hatchery ponds. The sum of nitrogen losses through volatilization, denitrification and sedimentation was 173.62 and 122.39 kg ha(-1), 54.86% and 62.29% of the total nitrogen input for P. vannanme ponds and M. nipponense hatchery ponds, respectively. Sediment accumulated 41.46 and 14.63 kg ha(-1) phosphorus, 74.37% and 64.85% of the total phosphorus input for P. vannanm ponds and M. nipponense hatchery ponds. Draining and seeping caused 40.06 kg ha(-1) nitrogen (12.66% of total nitrogen input) and 6.36 kg ha(-1) phosphorus (11.40% of total phosphorus input) loss to the surrounding water from P. vannanme ponds in 114 days; 30.14 kg ha(-1) nitrogen (15.34% of the total input) and 4.45 kg ha(-1) phosphorus (17.57% of the total input) to channel water from M. nipponense hatchery ponds in 87 days, respectively. Countermeasures for sustainable pond management include improving feeds and feeding, sediment treatments, machine aerating, chemicals with no pollution, and integrated fish-shrimp cultivation. Management of water resources for pond and methods to reduce nitrogen and phosphorus loading into surrounding water from drainage are elucidated.

The adsorption of lead and copper from aqueous solution on modified peat-resin particles.

Raw peat was modified with sulfuric acid, then mixed modified with resin to prepare the modified peat-resin particles. Using the batch experimental systems, the removal of heavy metals (copper and lead) on the modified peat-resin particles was investigated. The data of the adsorption isotherm could be fitted by the Langmuir equation well. The adsorption rate of heavy metals on modified peat-resin particles was very swift. The removal processes of heavy metals on modified peat-resin particles could be well described by pseudo-second order model. The adsorption rate of lead was affected by the initial heavy metal concentration, initial pH, particle size, agitation speed and particle mass. In the adsorption of heavy metals (lead and copper) on the modified peat-resin particles, ion exchange was the major reaction mechanism. Desorption data showed that the lead adsorbed by modified peat-resin particle could be desorbed by 0.5 N or 1.0 N HNO3. The desorption rate was swift. The experiments indicated that the modified peat-resin particles have great potential for the removal of heavy metals from wastewater.

Levels of urinary inter-alpha-trypsin inhibitor trimer as a function of age and sex-hormone status in males and females not forming stones.

OBJECTIVES: To determine if levels of inter-alpha-trypsin inhibitor (I alpha TI)-trimer differ in normal individuals based on age, gender or hormonal status, as the regulation of calcium oxalate (CaOx) crystallization inhibitors, e.g. by sex steroids, could be a mechanism contributing to the differences in CaOx urolithiasis between the sexes. SUBJECTS AND METHODS: Voided urine samples were collected from normal males and females. In Experiment 1 samples were grouped by gender and age, i.e. paediatric (PED) < or = 10 years, male (M) 21, female (F) 14; young adult (YGAD) 20-30 years, M 23, F 18; adults (AD), 35-50 year, M 25, F 13; adults aged > or = 60 years (> 60), M 24, F 16 (totals, M 93, F 61). In Experiment 2 samples were grouped by gender, age and hormonal status, i.e. PED, M 24, F 17; AD, M 24, F 22; > 60 and not on hormonal therapy, M 23, F 30; M > 60 and on androgen deprivation therapy (ANDEP) 18; and F > 60 on oestrogen supplementation, F+EST, 18 (total M 89, F 85). Levels of urinary I alpha TI-trimer were determined by immunoblotting and enhanced chemiluminescence, and relative densities of the bands determined. RESULTS: In both experiments the relative levels of I alpha TI-trimer were 2-7 times higher in M-PED than in all other groups of males (P < or = 0.007). Among adult males, I alpha TI-trimer levels were similar in all groups, including ANDEP (P > or = 0.9). There were no differences in the relative levels of I alpha TI-trimer among any of the groups of females, regardless of age or hormonal status (P > or = 0.7). CONCLUSIONS: In males a decrease in I alpha TI-trimer was associated with the onset of adulthood and entry into the 'stone-forming years'. Females did not show this decrease, and neither sex showed an increase in I alpha TI-trimer in the > 60 group, when the incidence of CaOx urolithiasis is supposedly declining. While changes in urinary I alpha TI-trimer levels in males may reflect maturational changes in the kidney, overall these data do not support the hypothesis that the age-related changes in the incidence of urolithiasis are paralleled by changes in the expression I alpha TI-trimer. Additionally, the sex steroids do not appear to acutely regulate the expression of I alpha TI-trimer in adults, making differences in I alpha TI-trimer levels unlikely to be the reason for the disparity in the incidence of CaOx urolithiasis between the sexes.

Serum cytokine levels are altered in patients with West syndrome.

The objective of this study is to explore the neuroimmunomodulator effect of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha and interferon (IFN)-alpha in West syndrome (WS). Twenty-three cases of WS (13 males and 10 females, aged 4-14 months old) who first visited and consisted from 10 cryptogenic and 13 symptomatic, were enrolled in this study. Double-antibody sandwich enzyme-linked immunosorbent assay was used to measure serum IL-2, TNF-alpha and IFN-alpha levels in 23 patients with WS and the data were compared to those of 15 healthy infants who were matched with regard to age and sex. Levels of all three cytokines were significantly higher in both cryptogenic and symptomatic WS groups than the control group. Serum IL-2 levels in symptomatic WS were significantly higher than that in cryptogenic WS. There was a positive correlation between IL-2 and TNF-alpha in both cryptogenic and symptomatic WS groups. The immune systems of patients with WS are in an activated state. An imbalance in cytokine levels may be involved in the immunopathology of WS.

Devazepide reversed effect of sincalide against morphine on rat jejunal activities.

AIM: To study the antagonism of sincalide to the effect of morphine and its mechanism. METHODS: The electrophysiologic and mechanic activities of rat jejunum in vitro were recorded. RESULTS: Acetylcholine (ACh, 150 nmol.L-1) increased the spike potential amplitude (SPA) and the number (SPN) of rat jejunum in vitro, followed by an increase of jejunal contraction amplitudes (CA), showing a positive correlation. Morphine 330 nmol.L-1 inhibited the potentiation of ACh, showing a negative correlation. Sincalide 0.7 nmol.L-1 antagonized the effects of morphine, i.e., the SPA and SPN were increased again, followed by an increase of CA. CCK-A receptor antagonist devazepide (10 nmol.L-1) reversed the antagonism of sincalide to the effect of morphine. CONCLUSION: Sincalide antagonized the effect of morphine which inhibited the potentiation of ACh on jejunal activities in vitro. The antagonistic effect of sincalide on morphine was mainly mediated by CCK-A receptor.

[The effect of RU486 on contractility of rabbit oviduct smooth muscle].

An investigation on the effect of RU486 on isolated ovicluct smooth muscle contraction of pseudopregant rabbits was carried out by using the mechanical-electrical transducer of Galson recorder. The results showed that: (1) RU486 acted directly on the oviduct smooth muscle by increasing contractile frequency, without changing tension and amplitude. This effect is similar to that found in the in vivo experiment. (2) RU486 partially inhibited Ca(2+)-induced smooth muscle contraction and also showed significant synergistic effect of Verapamil and antagonistic effect of NE on muscle contractility. However, RU486 is unable to exert any effect on Forskolin-stimulated contraction. Thus it appears that the RU486 effect on oviduct smooth muscle contraction is a result of affecting intracellular free calium, due possibly to interference of Ca2+ influx and/or endoplasmic reticulum Ca2+ release and Ca(2+)-Ip3 transducing mechanism.