[Application and value of body composition measurement in the evaluation of efficacy of bariatric and metabolic surgery].

The use of bariatric and metabolic surgery as a central treatment for obesity has been steadily increasing. BMI, as a widely used metric for assessing obesity, has considerable relevance in the field of metabolic research. However, its limitations, such as its inability to account for variations in fat distribution, remain a subject of considerable controversy. In recent years, there has been a surge of interest in the relationship between changes in body composition and the risk of metabolic disease. Consequently, the study of the effects of bariatric and metabolic surgery on changes in body composition has become a major focus of bariatric and metabolic surgery research. As a potential replacement for BMI, body composition measurements are expected to improve and standardize the assessment of the effectiveness of bariatric and metabolic surgery. This underscores the urgent need for the development of methods and standards for body composition measurement. This paper undertakes a comprehensive review of the existing evidence on the application of body composition measurement techniques for the efficacy evaluation of bariatric and metabolic surgery. The intent is to provide new insights and pave the way for the exploration of future research directions in this area.

[Effects of metabolic surgery on islet function in Asian patients with type 2 diabetes].

Type 2 diabetes is a high-profile global public health problem, particularly in Asia. The young age of onset, low body mass index, and early appearance of pancreatic islet dysfunction are characteristics of Asian patients with T2DM. Metabolic surgery has become the standard treatment for T2DM patients and can significantly improve T2DM through a variety of mechanisms including modulation of energy homeostasis and reduction of body fat mass. Indeed, restoration of islet function also plays an integral role in the remission of T2DM. After metabolic surgery, islet function in Asian T2DM patients has improved significantly, with proven short-term and long-term effects. In addition, islet function is an important criterion and reference for patient selection prior to metabolic surgery. The mechanism of islet function improvement after metabolic surgery is not clear, but postoperative anatomical changes in the gastrointestinal tract leading to a number of hormonal changes seem to be the potential cause, including glucagon-like peptide-1, gastric inhibitory polypeptide, peptide YY, ghrelin, and cholecystokinin. The authors analyzed the current retrospective and prospective studies on the effect of metabolic surgery on the islet function of Asian T2DM patients with a low BMI and its mechanism, summarized the clinical evidence that metabolic surgery improved islet function in Asian T2DM patients with a low BMI, and discussed its underlying mechanism. It is of great significance for realizing personalized and precise treatment of metabolic surgery and further improving its clinical benefits.

[Impact of hypoxic-ischemic injury on brain development in neonatal rats of different sexes].

Objective: To investigate the impact of hypoxic-ischemic brain injury (HIBI) on brain development in neonatal rats of different sexes. Methods: From January 1 to December 31, 2018, 60 7-day-old SD rats were randomly divided into HIBI-F group (20 rats), HIBI-M group (20 rats), and control group (20 rats, 10 females and 10 males). The animal model of HIBI was established with Rice-Vannucci method, with the rats' left common carotid artery double-ligated and severed. The rats were then placed in an incubator and exposed to a hypoxic gas mixture (8% O(2), 92% N(2)) for 90 minutes. No intervention was given to the control group. Two weeks after HIBI, the motor development was evaluated by footprint analysis, the residual brain volume was measured by brain magnetic resonance imaging (MRI), and the damage of synaptic ultra structure was analyzed by transmission electron microscope. One-way ANOVA or χ(2) test was used for inter-group statistical analysis, and paired sample t test was used to compare the bilateral step length and toe distance of rats in the same group. Results: The mortality rate of HIBI-F was significantly higher than that of HIBI-M (20%(4/20) vs. 10%(2/20), χ(2)=40.000, P=0.001). The right step length and toe distance in HIBI-M group and HIBI-F group were significantly shorter than those in control group ((7.5±0.3) cm and (7.9±0.5) cm vs. (8.2±0.5) cm, F=9.605, P<0.01, (0.9±0.1) cm and (1.0±0.0) cm vs. (1.1±0.1) cm, F=71.437, P<0.01). Besides, according to above data, the right step length and toe distance in HIBI-M group were significantly shorter than those in the HIBI-F group (both P<0.01). Furthermore, the right step length was significantly shorter than the left step length ((8.3±0.4) and (8.3±0.5) cm, t=5.289 and 10.580, P=0.001 and 0.010, respectively) and toe distance ((1.1±0.1) and (1.1±0.1) cm, t=7.953 and 6.435, respectively, both P<0.01) in both HIBI-M group and HIBI-F group. Similarly, the synaptic gap of the left precentral gyrus neurons was longer in HIBI-M group and HIBI-F group than that in control group ((23.4±1.3) and (19.7±1.6) nm vs. (18.9±0.6) nm, F=71.719, P<0.01), and also longer in HIBI-M group than that in HIBI-F group (t=7.645, P<0.01). Likewise, the residual brain volume in HIBI-M group and HIBI-F group was significantly less than that in control group ((67±4)% and (75±5)% vs. 100%, F=406.122, P<0.01), and the residual brain volume in HIBI-M group was significantly less than that in HIBI-F group (t=-5.281, P<0.01). Conclusions: Male neonatal rats are more vulnerable to HIBI and have severer subsequent brain injury and hemiplegia. Different treatment strategies for HIBI patients of different sexes should be developed.

Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients.

OBJECTIVES: The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). METHODS: The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. RESULTS: In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1ß-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. CONCLUSION: This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients.Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290-303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1.

[Establishment and optimization of hepatocyte steatosis model].

Objective: To establish a new model of hepatic steatosis cells by optimizing the original ethanol or high fat, the present study proposed an in vitro hepatocyte steatosis model for the study of fatty liver. Methods: Oil red O staining was used to observe the effects of fetal bovine serum, oleic acid and ethanol on lipid accumulation in human liver cell line L02 in a concentration- and time-dependent manner. RT-PCR was used to detect the mRNA expression levels of PPAR-γ and AP-2, and the suitable conditions for the establishment of hepatocyte steatosis model were screened out. A t-test was used for comparison between the two groups, and one-way Analysis of Variance (ANOVA) was used in more than three groups. Results: Oil red O staining showed the number of reddish-orange lipid droplets in L02 cells gradually increased with the increase of fetal bovine serum, oleic acid and ethanol in a concentration - and time-dependent manner. Compared with 0.00% oleic acid and 2% ethanol, the count value of red particle was 100.00% ± 17.63% at the beginning and after 24 h, 0.003% oleic acid and 2% ethanol jointly acted in L02 cells. After incubation for 48 hours with 2% ethanol and serum-free DMEM medium, the accumulation of lipid droplets was the highest with a count value of 802.38%+71.06%(t = 42.36, P < 0.001). RT-PCR analysis showed the lipid accumulation induced by this method was positively correlated with the mRNA expression of PPAR-γ and AP-2. Conclusion: L02 cells were successfully exposed to high fat and ethanol, and the hepatocyte steatosis model was established and optimized, suggesting that the occurrence of hepatic cell steatosis was related to the up-regulation of PPAR-γ and AP-2.

[Association of PD-1, TIM-3 and TREM-1 single nucleotide polymorphisms with pulmonary tuberculosis susceptibility].

Objective: To investigate the association of programmed cell death 1(PD-1), T cell immunoglobulin mucin 3 (TIM-3) and triggering receptor expressed on myeloid cells-1 (TREM-1) genes polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and of community physical examination volunteers (health control group) was collected from Mar 2015 to Sep 2016. A total of 66 single nucleotide polymorphisms (SNP) in PD-1, TIM-3 and TREM1 sequences were selected and SNP genotype and allele frequency were analyzed using the next-generation sequencing technology. Association of these SNP with pulmonary tuberculosis susceptibility was investigated using linkage disequilibrium (LD) analysis and genetic models. Results: Among these 66 SNP, 24 SNP with Hardy-Weinberg equilibrium P (HWE-P) value <0.001 or minimum allele frequency (MAF) <0.05 were kicked out. The remaining 42 SNP were analyzed with LD analysis and genetic models. There was no significant difference in genotype frequencies between pulmonary tuberculosis group and health control group (all P>0.05). Five SNP (rs41435650, rs28539662, rs13023138, rs75565781, rs36084323) in PD-1 were identified in a significant haplotype (TACGC) between pulmonary tuberculosis group and health control group (P=0.014). Among these haplotypes, strong LD was observed between rs28539662 and rs75565781 (r(2)=0.871), as well as rs36084323 (r(2)=0.864). Rs75565781 showed highest correlation with rs36084323 (r(2)=0.966). Conclusion: These SNP in PD-1, TIM-3 and TREM-1 genes are not associated with the susceptibility of pulmonary tuberculosis.

[Study on the changes of gonadotropin releasing hormone agonist in pinopodes].

Objective: To study the changes of gonadotropin releasing hormone agonist (GnRH-a) in pinopodes during luteal phase and to explore the possible mechanism of GnRH-a in luteal phase support of assisted reproductive technology (ART). Methods: Totally 40 primary infertility women who were treated with ART due to male factors were enrolled, according to the order of the group they were randomly divided into experimental group and control group. On the 7th day after ovulation, the experimental group received a subcutaneous injection of 0.1 mg of GnRH-a, while the control group received a subcutaneous injection of placebo only (0.9% saline 2 ml), 3 days later they came to the clinic again. Serum estradiol and progesterone levels were measured before and after treatment in each group. Pinopodes were collected for electron microscopic examination. Levels of ER and PR were detected by western blot. Results: (1) There was no significant difference between the experimental group and the control group in the estrogen level before and after the treatment (all P>0.05). The level of progesterone in the experimental group after treatment [(66.8±14.9) nmol/L] was significantly higher than that before treatment(P<0.05); also significantly higher than the same period of the control group (P<0.05). (2) There was no significant difference in the expression of ER protein in the experimental group before and after treatment (P>0.05). The expression of PR in the experimental group after treatment was significantly lower than that before treatment (P<0.05); also lower than the same period of the control group (P<0.05). (3) Expression amount of pinopodes in the experimental group after treatment was significantly higher than that before treatment [65% (13/20) versus 25% (5/20), P<0.05], and the development trend was more mature [the percentage of maturation:75% (15/20) versus 35% (7/20), P<0.05]. Expression amount of pinopodes after treatment and the percentage of maturation in the experimental group were significantly higher than those in the same period of control group (P<0.05). Conclusion: GnRH-a in luteal phase support may play a role through the corpus luteum, which may promote the secretion of progesterone, downregulation of PR expression, promote the growth of pinopodes, and improve the endometrial receptivity.

[Effects of San-huang-sheng-fu oil on peripheral circulatory disorders and foot ulcers in diabetic rats and the mechanisms].

OBJECTIVE: To observe the effects of San-huang-sheng-fu oil (S) on peripheral circulatory disorders and foot ulcers in diabetic rats and the relevant mechanisms. METHODS: (1) Twenty-five Wistar rats were divided into non-diabetes (N), diabetes and sham treatment (DS), metformin (M), S, and combined treatment (CT) groups according to the random number table, with 5 rats in each group. Rats in group N were injected with sodium citrate buffer solution, while rats in the other 4 groups were injected with 10 mg/mL streptozotocin to induce diabetes. In post injection week (PIW) 3, feet of rats in all the 5 groups received an ice-cold stimulation to induce peripheral circulatory disorders. From PIW 9 to 12, rats in groups N and DS were gavaged with saline and applied with sesame oil on pelma of both hind limbs; rats in group M were gavaged with diluted M and applied with sesame oil on pelma of both hind limbs; rats in group S were gavaged with saline and applied with S on pelma of both hind limbs; rats in group CT were gavaged with diluted M and applied with S on pelma of both hind limbs. In PIW 9 before treatment (hereinafter referred to as before treatment) and post treatment week (PTW) 1, 2, and 3, plantar temperature and hot pain threshold of rats were detected by infrared thermometer and foot tester respectively. (2) Another 25 rats were divided and induced with diabetes (expect for group N) as above. In PIW 9, rats in the 5 groups were inflicted with foot ulcer in the left pelma of hind limb by steam and received the corresponding treatment. On post treatment day (PTD) 3, 7, 21, and 35, the general condition and area of wounds were observed and measured respectively. All the rats were sacrificed on PTD 35, and wound tissue was collected for histomorphological observation and determination of expressions of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) using HE staining and immunohistochemical staining respectively. Data were processed with analysis of variance for repeated measurement, one-way analysis of variance, and Bonferroni post hoc test. RESULTS: (1) The experiment of peripheral circulatory disorders in diabetes. Compared with the plantar temperature of rats in group N, except for that in group CT in PTW 2 and groups M, S, and CT in PTW 3 (with t values from 0.258 to 2.647, P values above 0.05), the plantar temperature of rats with diabetes in the 4 groups at each time point was lowered significantly (with t values from 2.811 to 6.066, P values below 0.05). Compared with the plantar temperature of rats in group DS, except for that in group CT in PTW 2 and 3 significantly increased (with t values respectively 3.419 and 2.863, P values below 0.05), the plantar temperature of rats in groups M, S, and CT showed no significant difference at each time point (with t values from 0.128 to 1.654, P values above 0.05). The plantar hot pain threshold of rats was significantly decreased in group N than in the other 4 groups before treatment and group S in PTW 1 (with t values from 2.836 to 4.456, P values below 0.05). The plantar hot pain thresholds of rats in groups M, S, and CT were close to the hot pain threshold in group DS (with t values from 0.312 to 1.611, P values above 0.05). (2) The experiment of diabetic foot ulcers. Edema existed in all the wounds of rats on PTD 3. The wound areas of all the rats continued to increase with swelling and scar formation on PTD 7. On PTD 21, the scar of rats in groups N, S, and CT fell off; the wounds of rats in group DS were still swollen; scar of rats did not fall off with dark red in the skin around the wound in group M. On PTD 35, wounds of rats in groups N, S, and CT were nearly healed; while wounds of rats in groups DS and M were still swollen and the scar around the wound failed to fall off. On PTD 3 and 7, the wound areas of rats with diabetes in the 4 groups were close to those in group N (with t values from 0.111 to 1.476, P values above 0.05). On PTD 21, the wound area of rats in group DS was significantly larger than that in group N (t=5.502, P<0.01), while the wound areas of rats with diabetes in the other 3 groups were close to the area in group N (with t values from 0.544 to 1.676, P values above 0.05). On PTD 21, the wound area of rats in group M was close to that in group DS (t=1.895, P>0.05), while the wound areas of rats in groups S and CT were significantly smaller than the area in group DS (with t values respectively 5.809 and 3.426, P<0.05 or P<0.01). On PTD 35, the wound areas of rats in groups DS and M were significantly larger than the area in group N (with t values respectively 8.495 and 4.108, P values below 0.01), while the wound areas of rats in groups S and CT were close to the area in group N (with t values respectively 0.291 and 2.195, P values above 0.05). On PTD 35, the wound area of rats in group M was close to that in group DS (t=0.897, P>0.05); while the wound areas of rats in groups S and CT were significantly smaller than the area in group DS (with t values respectively 6.923 and 6.583, P values below 0.01). On PTD 35, the structures of wound tissue were in better integrity with less inflammatory cells and more regularly arranged collagen fibers around the wounds of rats in groups N, S, and CT than in groups DS and M. On PTD 35, the expression levels of COX-2 and VEGF in the wounds of rats in group DS [respectively (222±89)% and (55±12)%] were close to those in group M [respectively (137±24)% and (94±36)%, with t values respectively 3.046 and 2.653, P values above 0.05]. On PTD 35, the expression level of COX-2 in the wounds of rats in group DS was significantly higher than the expression levels of COX-2 in groups N, S, and CT [respectively (100±35)%, (91±42)%, and (109±17)%, with t values from 4.039 to 4.653, P values below 0.01], while the expression level of VEGF in the wounds of rats in group DS was significantly lower than the expression levels of VEGF in groups N, S, and CT [respectively (100±28)%, (143±12)%, and (120±13)%, with t values from 3.363 to 5.905, P<0.05 or P<0.01]. CONCLUSIONS: S can improve the plantar temperature decrease and pain dysesthesia of rats caused by diabetic peripheral circulatory disorders. It also can promote wound healing of diabetic foot ulcers in rats with down-regulation of COX-2 and up-regulation of VEGF.

Characterization of Complete Genome Sequences of a Porcine Endogenous Retrovirus Isolated From China Bama Minipig Reveals an Evolutionary Time Earlier Than That of Isolates From European Minipigs.

BACKGROUND: A porcine endogenous retroviruses (PERV) isolate, PERV-A-BM, was isolated from a Guangxi Bama minipig in China. METHODS: To understand its genetic variation and evolution, the complete PERV-A-BM genome sequences were determined and compared with isolates from different Sus scrofa breeds and porcine cell lines. A total of 69 nucleotide substitutions were found in the full-length genome, including 26 non-synonymous mutations. RESULTS: Phylogenetic trees based on the complete genome sequence as well as the gag, pol, and env gene sequences from 21 PERV isolates demonstrated that the PERV-A-BM was closely related to the EF133960 isolate from Chinese Wuzhishan miniature pigs inbred in Hainan, China, and distantly related to strains isolated from European-born pigs. CONCLUSIONS: The estimation of age in the proviral PERV-A-BM integrating into the host genome reveals that the age of PERV-A-BM is at least 8.3 × 10(6) years, an evolutionary time earlier than that of isolates from European-born pigs.

Involvement of endoplasmic reticulum stress in the necroptosis of microglia/macrophages after spinal cord injury.

Microglia/macrophages play a crucial role in inflammation after spinal cord injury (SCI). Although extensive studies have been performed on the mechanisms of microglia/macrophage activation and recruitment, how microglia/macrophages are eliminated remains unclear. In the present study, we observed a high-level expression of mixed lineage kinase domain-like protein (MLKL), a key molecule in the execution of necroptosis, in microglia/macrophages after SCI in mice. In vivo PI-labeling and Necrostatin-1 treatment confirmed the necroptosis of microglia/macrophages. Interestingly, our electronic microscopic (EM) study revealed that MLKL localized not only at the membrane but also on the endoplasmic reticulum (ER) of necroptotic microglia/macrophages. Furthermore, receptor-interacting protein 3 (RIP3), another necrosome component, was also found on the ER of necroptotic microglia/macrophages. And Glucose-regulated protein 78 (GRP78), an ER stress sensor, was up-regulated in MLKL-positive microglia/macrophages after SCI, suggesting a possible link between necroptosis and ER stress. In vitro, oxygen-glucose deprivation (OGD) stress induced ER stress and necroptosis in microglia. Inhibiting ER stress by 4-phenylbutyrate (4-PBA) significantly blocked the OGD-induced necroptosis of microglia. In the end, our data showed that, GRP78 and phosphorylated MLKL were co-expressed by the microglia/macrophages in the injured human spinal cord. Taken together, these results suggested that microglia/macrophages undergo an ER-stress involved necroptosis after SCI, implying that ER stress and necroptosis could be manipulated for modulating inflammation post-SCI.

Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor.

This study was designed to investigate the relationship of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) to invasion and metastasis of hepatocellular carcinoma (HCC). The expression of uPA, uPAR, and PAI-1 in HCC was determined by immunohistochemistry, Northern blot, and an LCI-D20 nude mouse metastatic model of HCC. The overexpression of uPA, uPAR, and PAI-1 was found in HCC, especially in the patients with portal cancer embolus, tumor invasion, and metastasis. Immunohistochemistry results showed that the rate of positive staining of uPA, uPAR, and PAI-1 were higher in HCC than those in the control groups consisting of cancer-adjacent tissue and normal liver tissue. In the case of HCC invasion, positive uPA and uPAR were seen in 16 and 19 out of 22 patients, respectively (P<0.01 and P<0.001, respectively, as compared with the patients without invasion). In those with portal cancer embolus and tumor metastasis, positive uPAR was eight out of eight and six out of six patients. In those with tumor recurrence, positive uPAR was 15 out of 17 patients (P<0.01 vs. no recurrence). In patients who died within 2 years after surgery, positive uPAR was 12 out of 12 patients (P<0.01 vs. survival), and positive PAI-1 was nine out of 12 patients (P<0.05 vs. survival). In those in which uPA, uPAR, and PAI-1 were all positive staining, stronger cancer invasiveness and higher mortality were found (P<0.05 vs. patients with all negative staining). In 30 patients tested with Northern blot analysis, the results were similar to those tested with immunohistochemistry. Higher expression of uPA mRNA and PAI-1 mRNA were detected in tumor tissues and embolus. In the patients with positive signals of uPA mRNA and PAI-1 mRNA, invasive cases were found in seven out of 19 and eight out of 18 patients, respectively, which were significantly higher than those showing negative signals (P<0.05). In the LCI-D20 nude mouse metastatic model of HCC (MMHCC), PAI-1 activity in plasma and tumor tissue increased with tumor growth, invasion, and metastasis. At an advanced stage of MMHCC, PAI-1 activity rose to 15.4+/-0.7 Au/ml in plasma and 0.8+/-0.3 Au/mg in tumor extracts, which was significantly higher than 6.2+/-1.8 Au/ml in plasma and 0.4+/-0.1 Au/mg in extracts at an early stage (P<0.05). PAI-1 activity related to the changes of serum AFP and tumor progress were r = 0.9544 and r = 0.9648, respectively (P<0.05). The data suggest that the expression of uPA, uPAR, and PAI-1 is increased in HCC, and related to the invasiveness, metastasis, and prognosis of HCC.

The effects of aerosolized dextran in a mouse model of Pseudomonas aeruginosa pulmonary infection.

Airway infections initiated by the interaction of bacterial adhesins with carbohydrate receptors can be potentially prevented by nontoxic carbohydrate inhibitors. Intranasal inoculation of neonatal mice with Pseudomonas aeruginosa PAO1 caused pneumonia in 55% of control mice but in only 13% of mice inoculated 2 h after dextran inhalation (P<.001) and in 28% inoculated 4 h after dextran inhalation (P=.02). PAO1 adherence to epithelial cells was inhibited by 50% in the presence of dextran. Dextran was well distributed throughout the airways and stimulated tumor necrosis factor-alpha production in murine lungs but not interleukin-8 production by human epithelial cell lines. Phagocytosis of PAO1 was not affected by dextran nor was killing by human neutrophils diminished. Administration of dextran by aerosol may prevent murine pneumonia by impeding bacterial access to epithelial receptors and by stimulation of the immune functions of the epithelium.

Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study.

Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.

Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers. Women and Infants Transmission Study.

To determine if hepatitis C virus (HCV) infection affects vertical transmission of human immunodeficiency virus (HIV), 487 HIV-infected pregnant women in the prospective, multicenter, Women and Infants Transmission Study had HCV antibody (anti-HCV by second-generation ELISA) and HCV RNA (by quantitative polymerase chain reaction) measured in peripartum maternal plasma; 161 (33%) were anti-HCV-positive. HIV vertical transmission occurred from 42 HCV-infected mothers (26.1%) versus 53 HCV-uninfected mothers (16.3%; odds radio [OR], 1.82; P = .01). In a logistic regression model that included maternal drug use, a potential confounder, HCV infection was marginally associated with perinatal HIV transmission (OR, 1.64; P = .05), whereas drug use was not. Women who transmitted HIV had higher levels of HCV RNA (median, 721,254 copies/mL) than those who did not (337,561 copies/mL; P = .01). Maternal HCV infection is associated with increased HIV vertical transmission. Further studies are needed to ascertain if HCV directly affects perinatal HIV transmission or is a marker for another factor, such as maternal drug use.

Dideoxyinosine-induced pancreatitis in human immunodeficiency virus-infected children.

Dideoxyinosine (ddI) is a widely used antiretroviral agent in treatment of HIV infection. Pancreatitis is a serious side effect. Two cases are reported, one with rapid development of a pseudocyst.

Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection.

We sought to identify which Pseudomonas aeruginosa products are involved initiating respiratory tract infection. Defined mutants derived from strain PAO i.e., PAOR1 (lasR),PAO-pmm (algC) (an LPS mutant), and AK1152 (which is Fla- and lacks functional pili), were significantly less virulent than PAO1 in a BALBc/ByJ neonatal mouse model of infection as measured by their abilities to cause acute pneumonia, bacteremia, and death. All three mutants were also less adherent to epithelial cells in an in vitro binding assay. PAOR1 and AK1152 were less able to elicit epithelial production of interleukin-8 than PAO1. LasR was found to be required for the optimal expression of neuraminidase under conditions of increased osmolarity, as might be present in certain pathological conditions. PAO-exsA::omega,, which lacks exoenzyme S expression, was fully virulent, causing at least as much pathology as PAO1. The expression of several P. aeruginosa virulence factors appears to be required to establish pulmonary infection in the neonatal mouse.

Treatment of intractable gastrointestinal manifestations of chronic granulomatous disease with cyclosporine.

Gastrointestinal manifestations of chronic granulomatous disease of childhood include granulomatous inflammatory bowel disease. Severe colitis and perirectal disease developed in a 12-year-old boy with chronic granulomatous disease while he was receiving interferon gamma therapy. The boy had a deficiency of the 22 kd light chain of the cytochrome b heterodimer. After conventional medical therapy proved to be ineffective, a rapid clinical response was obtained to cyclosporine.

Aromatase activity in the perinatal rat forebrain: effects of age, sex and intrauterine position.

Sex and regional differences in aromatase activity were characterized in brains of rats sacrificed on embryonic days 18 (E18) and 20 (E20) and on postnatal days 2, 4 and 13 (D2, D4, D13). Aromatase activity was measured in vitro in homogenates of the hypothalamus/preoptic area (HPOA) and temporal lobe (TL) from individual rats, using [3H]19-hydroxyandrostenedione as substrate in the presence of NADPH. The apparent Km of aromatase for 19-hydroxyandrostenedione in TL at D4 was similar in males (34 nM) and females (22 nM,). Aromatase activity in the HPOA was highest prenatally (E18) and gradually declined to low levels by D13. Aromatase activity in the TL remained constant from E18 to D2, increased significantly on D4, and subsequently declined to low levels by D13. The level of aromatase activity was significantly greater in males than in females on E18 and D4 in the HPOA and on D4 in the TL. Differences in aromatase activity within regions of the HPOA were studied at E20 and D4. At both ages, the activity was highest in the preoptic area, lower in the anterior hypothalamus (AH), and lowest in the posterior hypothalamus. Aromatase activity was significantly higher in males than in females in the AH, but only on D4. The contiguity of males in utero was not correlated with aromatase activity in brain regions of adjacent female fetuses. The present results indicate that significant sex differences in aromatase activity exist in specific brain regions only at discrete times during perinatal development.(ABSTRACT TRUNCATED AT 250 WORDS)