Glycemic variability leads to higher levels of auto-oxidized oxysterol species in patients with type 1 diabetes mellitus.

PURPOSE: Hyperglycemia and glycemic variability (GV) are associated with oxidative stress in patients with diabetes mellitus (DM). Oxysterol species, produced by the non-enzymatic oxidation of cholesterol, are potential biomarkers of oxidative stress. This study examined the relationship between auto-oxidized oxysterols and GV in patients with type 1 DM. METHODS: Thirty patients with type 1 DM using a continuous subcutaneous insulin infusion pump therapy and a healthy control group (n = 30) were included in this prospective study. A Continuous Glucose Monitoring System device was applied for 72 h. Blood samples were taken for oxysterols produced by non-enzymatic oxidation [7-ketocholesterol (7-KC) and cholestane-3ß, 5α, 6ß-triol (Chol-Triol)] levels at 72 h. Short-term glycemic variability parameters, mean amplitude of glycemic excursions (MAGE), the standard deviation of glucose measurements (Glucose-SD), and mean of daily differences (MODD) were calculated with continuous glucose monitoring data. HbA1c was used to evaluate glycemic control and HbA1c-SD (the SD of HbA1c over the past year) for long-term glycemic variability. RESULTS: 7-KC and Chol-triol levels were significantly higher in the study group than in the control group. Strong positive correlations were found between 7-KC with MAGE(24-48 h) and Glucose-SD(24-48 h). 7-KC was positively correlated with MAGE(0-72 h) and Glucose-SD(0-72 h). No significant correlation was found between HbA1c and HbA1c -SD with oxysterol levels. The regression models showed that SD(24-48 h) and MAGE(24-48 h) predicted 7-KC levels while HbA1c did not. CONCLUSIONS: Glycemic variability leads to higher levels of auto-oxidized oxysterol species in patients with type 1 DM independent of long-term glycemic control.

Stratum corneum hydration in healthy adult humans according to the skin area, age and sex: a systematic review and meta-analysis.

Stratum corneum (SC) hydration is one of the most important skin biophysical parameters, which is affected by age, sex and anatomic site. We conducted a systematic review and meta-analysis to provide detailed information on baseline values of SC hydration in healthy human adults, according to the skin area, age and sex. The databases Medline, Embase, Web of Science and Scopus were searched for primary reports, with in vivo corneometry measurements, which were conducted on disease-free skin of human subjects, aged 18+ years in English. Risk of bias was evaluated using the critical appraisal tools for JBI Systematic Reviews, and only low-risk studies were selected. The comparison was performed in each skin area between males and females and also between young- and middle-age subjects. Among 323 Retrieved titles, full texts of 259 articles were read, and 240 studies were excluded due to unclear or insufficient reporting of SC hydration, as well as high or medium risk of bias. 19 studies (including 113 records) providing data about SC hydration in 12 skin areas were included in the final data synthesis. Pooled sample sizes ranged from n = 32 for lips to a maximum of n = 3202 for cheeks. The lowest hydration of 12.5 [95% CI 11.05-13.94] was reported for the back, and the highest hydration of 64.34) [95 CI% 62.07-64.59] for the periorbital area. Facial skin showed higher water content compared with other areas. There were also site-dependent differences in the hydration level of the facial skin. Comparisons between two age groups, and male and female participants, did not show any statistically significant differences. The main limitation was we included studies using only one measurement device. The quality of reporting SC hydration in humans should be increased in future studies.

Oxysterol species: reliable markers of oxidative stress in diabetes mellitus.

PURPOSE: To assess the plasma oxysterol species 7-ketocholesterol (7-Kchol) and cholestane-3ß,5α,6ß-triol (chol-triol) as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus (DM). METHODS: In total, 26 type 1 and 80 type 2 diabetes patients, along with 205 age- and gender-matched healthy controls, were included in this study. Oxysterols were quantified by liquid chromatography coupled with tandem mass spectrometry and N,N-dimethylglycine derivatization. Correlations between oxysterols and clinical/biochemical characteristics of the diabetes patients, and factors affecting 7-Kchol and chol-triol, were also determined. RESULTS: Plasma 7-Kchol and chol-triol levels were significantly higher in type 1 and type 2 diabetes patients compared to healthy controls (P < 0.001). Significant positive correlations were observed between oxysterol levels and levels of glycated hemoglobin (HbA1c), glucose, serum total cholesterol, low-density lipoprotein, very-low-density lipoprotein, and triglycerides, as well as the number of coronary risk factors. Statins, oral hypoglycemic agents, and antihypertensive agents reduced the levels of oxysterols in type 2 diabetes patients. Statin use, HbA1c levels, and the number of coronary risk factors accounted for 98.8% of the changes in 7-Kchol levels, and total cholesterol, smoking status, and the number of coronary risk factors accounted for 77.3% of the changes in chol-triol levels in type 2 diabetes patients. CONCLUSIONS: Plasma oxysterol levels in DM, and particularly type 2 DM, may yield complementary information regarding oxidative stress for the clinical follow-up of diabetes patients, especially those with coronary risk factors.

Histamine metabolism and transport are deranged in human keratinocytes in oral lichen planus.

BACKGROUND: Recent reports have indicated that nonimmune cells can produce low concentrations of histamine. This observation, together with the discovery of the high-affinity histamine H4 receptor (H4 R), has added additional layers of complexity to our understanding of histamine signalling. Human oral keratinocytes (HOKs) possess a uniform H4 R pattern, which is deranged in oral lichen planus (OLP). OBJECTIVES: To investigate histamine metabolism and transport in HOKs of healthy controls and patients with OLP. METHODS: Tissue sections and cultured primary HOKs were studied using immunostaining, quantitative real-time polymerase chain reaction and confocal microscopy. Histamine levels were analysed using high-performance liquid chromatography. RESULTS: l-histidine decarboxylase (HDC) and organic cation transporter (OCT)3 were increased in mRNA and protein levels in patients with OLP compared with controls. In contrast, histamine N-methyltransferase (HNMT) immunoreactivity was decreased in OLP. OCT1/OCT2 and diamine oxidase were not detectable in either tissue sections or in HOKs. Immunolocalization of HDC and OCT3 in HOKs revealed moderate-to-high expression within cytoplasm and cell boundaries. Stimulation with lipopolysaccharide (LPS) or interferon-γ upregulated HDC-gene transcript in HOKs, whereas this was downregulated with high histamine concentration and tumour necrosis factor-α. LPS induced a dose-dependent release of low histamine in HOKs, while high histamine concentration downregulated epithelial adhesion proteins. CONCLUSIONS: HOKs are histamine-producing cells. They release histamine via OCT3 channels in concentrations too low to activate the classical low-affinity H1 R and H2 R, but high enough to stimulate the high-affinity H4 R in autocrine and paracrine modes. The substantially deranged histamine metabolism and transport in OLP could, in part, contribute to the disease pathogenesis.

Infection and apoptosis associated with inflammation in periodontitis: An immunohistologic study.

OBJECTIVE: Evidence of increased apoptosis is observed in periodontitis and may be associated with destruction of the periodontal tissue caused by the increased cell death, with the release of danger signals and subsequent stimulation of the proinflammatory processes. However, the exact mechanisms associated with these processes remain unclear. This study aimed to investigate the presence of the periodontal pathogen Treponema denticola, apoptosis, high mobility group box 1 as a damage-associated molecular pattern, and several inflammatory markers in periodontitis and gingivitis subjects. MATERIALS AND METHODS: Soft tissue specimens from gingival tissues of periodontitis and gingivitis patients were used for immunohistochemical and immunofluorescence staining of T. denticola chymotrypsin-like proteinase (CTLP), apoptosis markers, high mobility group box 1, Toll-like receptor 4, inflammatory cell markers, and proinflammatory cytokines. RESULTS: Treponema denticola was detected in all periodontitis-affected tissues. This was associated with a significant increase in the number of apoptotic cells, including macrophages, alterations in the expression of high mobility group box 1 and its receptor, and increased levels of proinflammatory cytokines compared with gingivitis. CONCLUSIONS: In summary, the presence of T. denticola (especially its CTLP), apoptosis, high mobility group box 1, and inflammatory markers suggests their potential involvement in the pathogenesis of periodontitis.

Expression of cathepsin K in periodontitis and in gingival fibroblasts.

OBJECTIVE: To study non-osteoclastic sources of cathepsin K in periodontitis. MATERIALS AND METHODS: Tissue samples were obtained from 10 otherwise healthy periodontitis pati-ents during routine periodontal flap operations and 10 systemically and periodontally healthy individuals who underwent extraction operations for retained third molars. Methods used were immunohistochemistry, image analysis, immunofluorescence double-staining, gingival fibroblast culture, tumour necrosis factor-α (TNF-α) stimulation and Western blotting. RESULTS: Macrophage-like cells, fibroblast-like cells, vascular endothelial cells and gingival epithelial cells were more intensively stained for cathepsin K and also more frequent in periodontitis than in controls (665 ± 104 vs 258 ± 40 cells mm(-2) , P < 0.01). Some cathepsin K(+) cells in periodontal tissues were CD68(+) , but some were CD68(-) and probably fibroblasts. Indeed, in gingival fibroblast culture, resting fibroblasts released cathepsin K, more 43 kD procathepsin K than 29 kD active cathepsin K. TNF-α increased the release of the activated cathepsin K 4- to 5-fold. CONCLUSIONS: Results suggest that GCF-cathepsin K is not only osteoclast-derived, but in periodontitis, also other cells contribute to it. GCF-cathepsin K, perhaps together with intracellular, lysosomal collagenolytically active cathepsin K in fibroblasts, macrophages and gingival epithelial cells, can contribute to the loss of attachment and destruction of the periodontal ligament.

Increased beta 2 defensin in recurrent aphthous ulcer.

OBJECTIVES: It was hypothesized that beta 2 defensin (BD-2) is increased in RAU lesions compared with healthy controls to promote anti-microbial host defence. METHODS: RAU and control mucosa samples were subjected to quantitative real-time PCR and immunostained for BD-2, CD68, mast cell tryptase and 4-hydroxynonenal (4HNE). The effect of tumour necrosis factor-α (TNF-α) ± interleukin-17C (IL-17C), without and with vitamin K3, was studied on BD-2 expression in epithelial SCC-25 cells. RESULTS: Although BD-2 mRNA did not differ between healthy and RAU mucosa, BD-2 stained strongly in acute-phase RAU epithelium (P = 0.001). In controls, subepithelial BD-2(+) cells were mast cells and macrophages, whereas in RAU, most infiltrating leucocytes were BD-2(+) (P = 0.004). In cell culture, BD-2 was increased 124-fold by TNF-α (P < 0.0001) and 208-fold synergistically together with IL-17C (P < 0.0001). 4HNE staining of RAU epithelium was not significantly increased, and vitamin K3-induced reactive oxygen species (ROS) did not affect BD-2. CONCLUSIONS: Anti-microbial BD-2 was not affected by oxidative stress but was highly increased in the epithelial and immigrant cells in the acute-phase RAU lesions, probably in part synergistically by TNF-α and epithelial IL-17C, which are known to be induced by activation of danger-signal receptors by pathogen- and/or damage-associated molecular patterns.

Histamine H4 receptor in oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines. MATERIALS AND METHODS: Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes. RESULTS: H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts. CONCLUSION: Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.

Bioleaching of sewage sludge for copper extraction using Acidithiobacillus thiooxidans: Optimization and ecological risk assessment.

In this study, Acidithiobacillus thiooxidans was used for the bioleaching of copper (Cu) from sewage sludge. In order to find optimization conditions, three factors including solid-to-liquid ratio (S/L) (0.01-0.2 %(w/v)), initial element sulfur (S0) (1-10 g/L), and initial pH (1-3) have been investigated. Based on response surface methodology (RSM) determined a significant reduced quadratic model with a p-value of 0.0022 (<0.05 significant level). The maximum Cu recovery was 85.3% in the optimum condition of S/L = 0.16% (w/v), S0 = 8.2 g/L, and pH = 1.4. Furthermore, a kinetic study based on a shrinking core model was performed and the result showed that chemical reaction was rate limiting in the extraction. Toxicity Characteristic Leaching Procedure (TCLP) results after bioleaching showed the bioleaching process detoxified sludge and the bioleached sludge residue was well within the regulatory limits for disposal. The germination seed with adding bioleached and unbioleached sludge to the soil was determined. Various parameters such as Germination Index (GI), Tolerance Index (TI), Vigor Index (VI), and stem length showed that the sewage sludge indices significantly increased than the sample soil with unbioleached sludge.

Monitoring of Newcastle Disease Virus Vaccine Strain Replication in Embryonated Chicken Eggs by Reverse Transcription-Polymerase Chain Reaction.

The knowledge of virus and replication kinetics plays a key role in developing a vaccine. This study aimed to monitor the replication process and determine the best harvesting time of the Newcastle disease virus (NDV) V4 vaccine strain in the allantoic fluids of specific pathogen-free (SPF)-embryonated chicken eggs (ECEs) by reverse transcription-polymerase chain reaction (RT-PCR), hemagglutination (HA), and egg infective dose 50% (EID50) tests. For this purpose, the V4 vaccine strain of the virus was intra-allantoically inoculated into 96 10-day-old SPF-ECEs at the rate of 0.1 mL/ECE. The allantoic fluids of the inoculated eggs were collected from six eggs at six-hour intervals up to 96 hours post-infection (hpi). The harvested suspensions were confirmed to contain the NDV by the mentioned serologic and molecular techniques. Based on the results, the virus was first detected at 36 hpi in ECEs by RT-PCR. The peak of HA and EID50 titers in allantoic fluids started at 42 hpi, and the titers were at the highest level until the end of the experiment. The results indicated that the best virus harvesting time for the NDV V4 vaccine strain in ECEs is between 42-60 hpi. These findings pave the way for adequate and enhanced production rate, immunogenicity, and cost-related parameters in the V4 Newcastle vaccine development.

Effect of various ratios of carbohydrate-protein supplementation on resistance exercise-induced muscle damage.

AIM: Previous studies have indicated that exercise-induced muscle damage might be attenuated by coingestion of protein and carbohydrate supplement. The purpose of this study was to compare the effect of three various ratios of carbohydrate-protein (CHO+PRO) supplements on resistance exercise-induced muscle damage indices. METHODS: Twenty-eight untrained male students voluntarily participated in this study and were randomly assigned to one of the four groups: 1) CHO+PRO 2:1 ratio, N.=7; 2) CHO+PRO 3:1 ratio, N.=8; 3) CHO+PRO 4:1 ratio, N.=7; 4) placebo group, N.=6. They performed a single bout of resistance exercise (whole body: 3 set×8-10 reps with 70-75% 1RM), with eccentric concentration. Every group consumed prepared CHO/PRO beverages (9% concentration, 10 mL/kg/bw-1 at different ratios) or the same amount of placebo beverage before and in 15 min intervals during exercise. Blood samples were taken before the exercise bout and also at 1 and 24 h post-exercise. In addition, muscle soreness scores were recorded before and 1, 24, and 48 h postexercise. Repeated measures ANOVA (between-within design) and Bonferroni post hoc test were used to analyze dependent measures (α=0.05). RESULTS: Serum creatine kinase (CK) and myoglobin (Mb) increased in all groups compared with pre-exercise but the significant difference among groups was observed in 24 h postexercise, in a way that both CK and Mb levels were higher in placebo group. Muscle soreness increased for all groups from pre to postexercise, but there was not any significant difference among groups at any time point. CONCLUSION: Findings of this study showed that CHO+PRO decreased serum CK and Mb at 24 h post exercise, but did not affect muscle soreness at any time points after exercise. Moreover, there were no significant differences between various ratios of CHO-PRO supplementation.

Assessment of inceptisols soil quality following long-term cropping in a calcareous environment.

The combination of morphological, clay mineralogy, physicochemical, and fertilitical properties of inceptisols were compared for monitoring soil quality response following long-term agricultural activities. For this target, fifty-nine paired surface soils belonging to five subgroups of inceptisols from the major sugar beet growing area and the adjoining virgin lands were described, sampled, and analyzed. The soils were alkaline and calcareous as characterized by high pH, ranging from 7.2 to 8, and calcium carbonate equivalent, ranging from 60 to 300 g kg(-1). Following long-term sugar beet cultivation, morphological properties modifications were reflected as weakening of structure, hardening of consistency, and brightening of soil color. Although, the quantity of clay minerals did not significantly change through long-term cropping, some modifications in the XRD pattern of illite and smectite were observed in the cultivated soils compared to the adjoining virgin lands mainly as a result of potassium depletion. Without significant variation, sand content decreased by 4-55% and silt and clay increased by 3-22% and 2-15%, respectively, in the cultivated soils than to that of the virgin lands. Both negative and positive aspects of soil quality were reflected regarding soil chemical and fertilitical properties and the role of negative effects far exceeded the role of positive effects. Typic calcixerepts was known to be more degraded through a significant decrease (P ≤ 0.001) in mean value of soil organic carbon (a drop of 24%), total N (a drop of 23%), available K (a drop of 42%), exchangeable K (a drop of 45%), potassium adsorption ratio and potassium saturation ratio (a drop of 44% and 42%, respectively) and a significant increase (P ≤ 0.001) in EC (a rise of 53%). Soil quality index, calculated based on nine soil properties [coarse fragments, pH, SOC, total N, ESP, exchangeable cations (Ca, Mg, and K), and available phosphorus], indicated that 60% of the all soil types studied had negative changes, 20% had positive changes, and 20% produced no changes in soil heath.

The effect of posterior bite-plane on dentoskeletal changes in skeletal open-bite malocclusion.

With regard to the vertical problem of skeletal open-bite malocclusion, this study was undertaken to evaluate the effect of upper posterior bite-plane on the dentoskeletal changes of skeletal open-bite malocclusion. The material consisted of 23 patients, with skeletal open-bite in mixed dentition period. The patients were treated by upper removable posterior bite plane appliance. Before and after treatment lateral cephalogram were obtained. Certain angular and linear variables were measured. The pre-treatment and post-treatment measurements were compared using paired t-test to evaluate the significance of the results. There were significant changes in vertical incisor overlap following treatment with upper posterior bite plane. Increase of PFH, Jaraback index, UAFH/LAFH ratio were significant .There was significant decrease in SN-MP angle. The dentoalveolar heights of the upper and lower anterior segment were increased as well as the distance of the lower molars to mandibular plan. Only the maxillary first molar height did not change.

Impact of the uncontrolled leakage of leachate from a municipal solid waste landfill on soil in a cultivated-calcareous environment.

The heavy metal pollution generated by landfill leachate becomes increasingly concerning due to its potential to impact human health through the food chain. In the present study, the accumulation and potential health risk of heavy metals (Zn, Cu, Cd, Pb, and Ni) were investigated in a calcareous soil -wheat system affected by an uncontrolled landfill leachate. The results showed soils were significantly enriched by both the available and total fractions of the metals in the sequences of Zn > Pb > Ni > Cd > Cu and Cd > Zn > Ni > Pb > Cu, respectively. Nevertheless, only the Cd content exceeded the standard levels. For the various population groups, the mean hazard quotient (HQ) was lower than the unity, implying a lack of non-carcinogenic health risk for the local residents, while the average hazard index (HI) was 2.3 and 1.1 for people aged 0-5 and 6-18 years, respectively, illustrating a moderate non-carcinogenic health risk for the two groups. Cd and Pb contributed the most to HI, followed by Cu, Zn, and Ni. In addition, the carcinogenic health risk of Cd, ranging from 1 × 10-5 to 1 × 10-6, showed a low potential risk in the different population groups exposed to wheat grains and decreased in the sequence of adult > population 6-18 years > population 0-5 years. The findings of the study, which can be used in regions under similar environmental conditions, provide a valuable benchmark for the design of appropriate strategies to manage these agroecosystems by both local and national managers of such macrosystems.

Urologic complications in renal transplant recipients by donor type.

BACKGROUND AND PURPOSE: Reduced donor morbidity has been established after laparoscopic donor nephrectomy compared with open harvest, but differences in recipient outcomes remain less obvious. We compared the urologic complications in patients receiving kidneys procured by cadaveric, open, and laparoscopic harvest. PATIENTS AND METHODS: A retrospective study of all the kidney transplantations performed between January 1998 and December 2003 was undertaken to extract 100 consecutive patients in each group. All urologic complications were obtained and grouped by the type of donor procurement. RESULTS: Overall, 48 of the 276 transplant patients (17%) had urologic complications: 14% of the cadaveric-donor recipients, 20% of the open-donor recipients, and 18% of the laparoscopic-donor recipients. There were no ureteral complications in the laparoscopic group. CONCLUSIONS: Laparoscopically procured donor kidneys were associated with significantly fewer recipient ureteral complications than open cadaver or live-donor procurement.

Sjögren's syndome and extragonadal sex steroid formation: a clue to a better disease control?

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphoplasmacytoid focal adenitis leading to mucosal dryness, with 9:1 female dominance and peak incidence at menopause. Due to autoimmune adenitis it can be speculated that the normal epithelial cell renewal has failed, possibly as a result of local intracrine failure to process dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). Local intracrine/-cellular DHT deficiency seems to predispose to SS if estrogens are low, in menopausal women and in men. This intracrine failure could be the initial noxious stimulus, factor X, initiating the development of SS. Abnormal release and presentation of exocrine gland-derived antigens (Ag-epitopes), in a complex with major histocompatibility complex class II (MHC II), by migratory dendritic cells (DC) activates T-cells in the regional lymph nodes. B-cells with the same specificity capture and present self-Ag to Th-cells which provide T-cell help. B-cells transform to plasma cells and start to produce autoantibodies (Ab) against these T-cell-dependent Ag. Ab against SS-A/Ro and SS-B/La ribonucleoproteins occur only in HLA-DQw2.1/DQw6 heterozygous individuals, but hY-RNA and RNA polymerase III transcripts in these Ag may in all SS patients stimulate toll-like receptors (TLR) 7 and 9 of the plasmacytoid DCs, because IFN-α and IFN-signature are produced. CD8+αEß7+cytotoxic T-cells activated via cross-presentation recirculate to attack intracrine-deficient, apoptotic epithelial cells expressing self-Ag on their surface. Exocrine glands fall into the sphere of mucosal/gut-associated lymphatic tissue. This together with immune complexes spreads the immunological memory/aggression to extra-glandular sites explaining the systemic nature of the syndrome. Secondary SS could be explained by disturbed lymphocyte recirculation. There is no conclusive evidence that SS in those few men affected is more severe than in women, suggesting that sex steroid endo-/intracrinology has its major impact on the target tissue, not on immune modulation. This article is part of a Special Issue entitled 'Essential role of DHEA'.

Epithelial Cell Apoptosis in Recurrent Aphthous Ulcers.

A recurrent aphthous ulcer (RAU) is a common inflammatory ulcerative lesion affecting oral mucosa. We studied the eventual apoptosis of epithelial cells from the point of view of ulcer and inflammation. RAU lesions and healthy mucosa samples were immunostained for caspase-3 and high-mobility group box 1 (HMGB1). DNA nicks were identified using TUNEL staining. We studied the effects of tumor necrosis factor α (TNFα) and interferon γ (IFNγ) on the toll-like receptor 2 and 4 (TLR2 and TLR4) expression of human oral SCC-25 keratinocytes. We also studied the effects of self-DNA, all-thiol-HMGB1, and disulfide-HMGB1 on epithelial cells, with or without IFNγ. At the edge of RAU lesions, all epithelial cell layers were caspase-3(+), TUNEL(+), and HMGB-1(+) and had widened intercellular spaces. In contrast, healthy epithelial cells were negative for caspase-3 and TUNEL staining. HMGB1 was seen in only the basal cell layers, and the cells retained close cell-to-cell contacts. Self-DNA increased TNF-α mRNA (P = 0.02) in SCC-25 cells. Both TNFα and IFNγ (P = 0.01) increased TLR2. Upon TNFα stimulation, SCC-25 cells lost their nuclear HMGB1 staining. HMGB1 did not increase IL-8, IL-6, or TNF-α mRNA in SCC-25 cells, which was unaffected by the presence of IFNγ. We conclude that in healthy epithelium, the most superficial cells at the end of their life cycle are simply desquamated. In contrast, RAU is characterized by top-to-bottom apoptosis such that dead cells may slough off, leading to an ulcer. Because of a lack of scavenging anti-inflammatory macrophages, apoptotic cells probably undergo secondary necrosis releasing proinflammatory danger signals, which may contribute to the peripheral inflammatory halo. This is supported by self-DNA-induced TNFα synthesis. In contrast to TLR4- and TLR2-binding lipopolysaccharide used as a positive control, disulfide-HMGB1 did not stimulate proinflammatory cytokines.

Maternal hypertension and spontaneous preterm births among black women.

OBJECTIVE: To examine effects of maternal hypertension on spontaneous preterm birth (birth at less than 37 weeks' gestation) among black women. METHODS: Using hospital discharge summary records from the National Hospital Discharge Survey between 1988 and 1993, we conducted a case-control study to assess the risk of spontaneous preterm birth among black women with chronic hypertension preceding pregnancy and pregnancy-induced hypertension. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Preterm births were almost two times more likely for women with pregnancy-induced hypertension (OR = 1.8; 95% CI, 1.5, 2.2), more than 1.5 times more likely for women with chronic hypertension preceding pregnancy (OR = 1.6; 95% CI, 1.3, 2.1), and more than four times more likely for women with pregnancy-aggravated hypertension (OR = 4.4; 95% CI, 2.9, 6.7) compared with normotensive women. Preterm births also were associated significantly with antepartum hemorrhage, poor fetal growth, marital status, and source of payment. The odds of preterm birth by maternal hypertension were increased among women with chronic hypertension and genitourinary infection, whereas the odds of preterm birth were reduced among women with pregnancy-induced hypertension and genitourinary infection. CONCLUSION: These findings are important in demonstrating the relation between type of hypertension in pregnancy and preterm birth. The relationships between maternal hypertension and preterm birth need to be further investigated to provide some guidelines in the management of hypertension in pregnancy and assessment of prenatal care compliance for black women, particularly when genitourinary infection is present.

Maternal hypertension and associated pregnancy complications among African-American and other women in the United States.

OBJECTIVE: To characterize maternal hypertension and related pregnancy complications among African-American and other women in the United States. METHODS: Using data from the National Hospital Discharge Survey, we analyzed the incidence and clinical spectrum of maternal hypertension among African-American women who delivered in hospital during 1988-1992. Maternal hypertension consisted of pregnancy-induced hypertension and chronic hypertension preceding pregnancy, including pregnancy-aggravated hypertension. Pregnancy-induced hypertension included preeclampsia, eclampsia, and transient hypertension. Incidence rates (per 1000 deliveries) and 95% confidence intervals (CI) were calculated by type of hypertension and demographic characteristics. Risk ratios and 95% CIs for adverse pregnancy outcomes among women with hypertension were also calculated. RESULTS: The overall incidence of all causes of maternal hypertension was 64.2, and of chronic hypertension preceding pregnancy it was 25.0 per 1000 deliveries among African-American women, an excess of 15.6 and 14.5 cases per 1000 deliveries, respectively, compared with rates for other women. The risks of preterm delivery and inadequate fetal growth were similarly increased for all hypertensive women, regardless of race. However, hypertensive African-American women were at a threefold greater risk of pregnancies complicated by antepartum hemorrhage, an association that was not observed, in other women. Development of preeclampsia and eclampsia irrespective of race was about four times higher among women with chronic hypertension preceding pregnancy than among those without chronic hypertension. CONCLUSION: The excess incidence of maternal hypertension, particularly chronic hypertension, may contribute to adverse maternal and fetal pregnancy outcomes and the disparity in outcomes observed between African-American and other women in the U.S. These findings provide a specific focus for further clinical outcomes research and assessment of prenatal management in African-American women.