Trends in cigarette smoking among US adults with diabetes: findings from the Behavioral Risk Factor Surveillance System

BACKGROUND: Smoking substantially increases morbidity and mortality rates in people with diabetes. Previous studies have shown that the prevalence of smoking among people with diabetes is similar to that among people without diabetes. We sought to examine temporal trends in the prevalence of smoking among people with diabetes since 1990. METHODS: We analyzed data from the Behavioral Risk Factor Surveillance System for 1990-2001. RESULTS: The age-adjusted prevalence of smoking among adults with diabetes was 23.6% (men, 25.4%; women, 22.2%) in 1990 and 23.2% (men, 24.8%; women, 21.9%) in 2001. In comparison, the prevalence among participants without diabetes was 24.2% (men, 25.7%; women, 22.8%) in 1990 and 23.2% (men, 24.8%; women, 21.5%) in 2001. Thus, the prevalence of cigarette smoking was similar and remained stable from 1990 through 2001. Among participants with diabetes, significant decreases in the prevalence of smoking occurred among African Americans and those aged >/=65 years. CONCLUSIONS: New efforts and commitments to promote smoking cessation among people with diabetes are needed.     

Vaginal bleeding during pregnancy and preterm birth

This study investigated the relation between self-reported vaginal bleeding during pregnancy and preterm birth in a prospective cohort of 2,829 pregnant women enrolled from prenatal clinics between 1995 and 2000 in central North Carolina. The overall association between vaginal bleeding and preterm birth was modest (risk ratio (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.6). Bleeding in the first trimester only was associated with earlier preterm birth (< or =34 weeks' gestation) (RR = 1.6, 95% CI: 1.1, 2.4) and preterm birth due to preterm premature rupture of the membranes (PPROM) (RR = 1.9, 95% CI: 1.1, 3.3). Bleeding in both trimesters was associated with preterm birth due to preterm labor (RR = 3.6, 95% CI: 1.9, 6.8). Bleeding of multiple episodes, on multiple days, and with more total blood loss was associated with an approximate twofold increased risk of earlier preterm birth, PPROM, and preterm labor. In contrast, bleeding in the second trimester only, of a single episode, on a single day, and with less total blood loss was not associated with any category of preterm birth. Vaginal bleeding was not associated with preterm birth among African Amercians (RR = 1.2, 95% CI: 0.9, 1.7). This study indicates that more intense but not less intense bleeding is associated with earlier preterm birth and spontaneous preterm birth presenting as PPROM or preterm labor, and it suggests that bleeding is less predictive of preterm birth among African-American compared with White women.     

Smoking in Ontario schools: does policy make a difference?

OBJECTIVE: Studies in other countries have shown that school tobacco control policy has potential to prevent smoking uptake in adolescents. Since no Canadian research has studied this association, we assessed the statistical link between school tobacco policy and smoking status in Ontario elementary and secondary schools. METHODS: We conducted secondary analysis of data collected using the School Smoking Profile, a cross-sectional, self-report questionnaire. School policy variables were formed from five survey items concerning students' perceptions of school tobacco control policy. Smoking status was determined through self-report measures which had been validated by carbon monoxide testing. Logistic regression models used school policy variables to explain smoking status in elementary and secondary schools, controlling for school location, school size, and student's grade level. RESULTS: The smoking policy variables, rules and enforcement, explained smoking status after controlling for other variables. In elementary schools, perceptions of stronger enforcement reduced the odds of being a smoker (OR = 0.39, CI99 = 0.34-0.44). In secondary schools, enforcement lost its protective effect (OR = 1.05, CI99 = 1.00-1.10). In addition, student perceptions that rules were strong were indicative of increased smoking in secondary schools (OR = 1.32, CI99 = 1.27-1.37). DISCUSSION: Strong enforcement of school tobacco control policy appears to be effective in elementary schools but is not as helpful in secondary schools. Secondary school policymakers should consider modifying their sanctions to avoid alienating smokers.     

Lactational amenorrhea as a method of family planning in Egypt

Because of the potential importance of the lactational amenorrhea method (LAM) as a family-planning option in Egypt, we analyzed data from the 1995 Egyptian Demographic and Health Survey (EDHS) to study breastfeeding practices, use of contraception, reproductive history and sociodemographic factors for 5504 mothers with children under 3 years. According to the EDHS data, about 80% of Egyptian women breastfed for at least 6 months, and 40% breastfed for 15-18 months. Over half of breastfeeding mothers used no additional contraception. Thirty-six percent of mothers breastfeeding children younger than 6 months who reported using no additional contraception were exclusively breastfeeding and amenorrheic, but only 4% reported relying on breastfeeding for family planning. We also held eight focus group discussions with breastfeeding mothers from urban and rural Upper and Lower Egypt on their use of contraceptive methods, breastfeeding, lactational amenorrhea and LAM. Participants showed strong recognition of the contraceptive effects of breastfeeding but differed widely in their understanding of lactational infecundability and knowledge of LAM as a method. These results suggest that LAM would be widely acceptable to Egyptian women, but that an educational program about the method is needed.     

Duodenal ascorbate levels are changed in mice with altered iron metabolism

Ascorbate has long been thought to play an important role in intestinal iron absorption. The recent identification of a possible ascorbate-dependent duodenal ferric reductase suggests a role for intracellular ascorbate in the control of iron absorption. We set out to determine whether duodenal ascorbate concentrations are altered by treatments known to alter the rate of iron absorption and whether ascorbate levels affect duodenal reductase activity. Duodenal ascorbate was extracted and assayed by HPLC and/or a chemical assay. Ferric reductase was assayed in vitro with ferric nitrilotriacetate or nitroblue tetrazolium as substrates. Duodenal ascorbate concentrations were increased by iron deficiency, genetic hypotransferrinemia, and hypoxia. Parenteral iron overload increased iron stores but did not affect duodenal ascorbate concentrations. Hemolytic anemia induced in mice by phenylhydrazine injection also did not affect duodenal ascorbate concentrations. In vitro studies with incubated duodenum showed that decreased tissue ascorbate was associated with decreased mucosal ferric reductase activity, whereas incubation with dehydroascorbate prevented both the decrease in ascorbate concentration and reductase activity. Mouse duodenum ascorbate concentrations changed in response to treatments that altered iron absorption rates; in particular, ascorbate levels generally increased when iron absorption was increased by iron deficiency, hypoxia, or genetic hypotransferrinemia. We conclude that changes in ascorbate levels are associated with changes in ferric reductase activity. These findings are consistent with the proposal that duodenal ascorbate plays a role in intestinal iron absorption.     

The effects of three-piece or single-piece acrylic intraocular lens implantation on posterior capsule opacification

PURPOSE: To evaluate the development of posterior capsule opacification (PCO) in patients implanted with 5.5 mm optics, single-piece or three-piece acrylic intraocular lens (IOL) in cataract surgery prospectively. METHODS: This study was carried out on 267 eyes of 249 patients implanted with three-piece, 5.5 mm optics, acrylic IOL and 252 eyes of 244 patients implanted with single-piece, 5.5 mm optics, acrylic IOL by phacoemulsification technique between September 2001 and February 2003. A total of 519 eyes of 493 patients were prospectively evaluated for PCO development during the 25-month period. All the patients were analyzed periodically with anterior segment retroillumination photography. The data provided were analyzed with chi-square method. RESULTS: The results between the two groups for PCO development were not statistically significant. However, there was a prominent opacification of the posterior capsule where the optic and haptic junction of IOL was positioned in some patients implanted with single-piece IOL. During the follow-up period, no patients implanted with either three-piece or single-piece acrylic IOL required Nd:YAG laser capsulotomy. CONCLUSIONS: Biocompatibility and reduced rate of PCO development are among the leading features of new generation IOLs. The intracapsular implantation of 5.5 mm optics acrylic IOLs resulted in decreased incidence of PCO and therefore greater patient satisfaction. Further studies investigating the effects of IOL optics, haptic structure and length, capsulorrhexis size, and IOL material and design features on PCO development will clarify the subject.     

Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters

Several of the ATP-binding cassette (ABC) transporters confer resistance to anticancer agents and/or antiviral agents when overexpressed in drug-sensitive cells. Recently a MRP1 (ABCC1) tricyclic isoxazole inhibitor, LY475776 was shown to be a glutathione-dependent photoaffinity label of human MRP1 and showed poor labeling of murine mrp1, an ortholog that does not confer anthracycline resistance. In the present study, the specificity of LY475776 was examined for its ability to modulate or photolabel orthologs of MRP1 and several other drug efflux transporters of the ABC transporter family. LY475776 modulated MRP1 and Pgp-mediated resistance (MDR, ABCB1) in, respectively, HeLa-T5 and CEM/VLB(100) cells to both vincristine and doxorubicin. LY475776 photolabeled 170kDa Pgp and was inhibited by the potent Pgp inhibitor LY335979 (Zosuquidar.3HCl). The labeling of the 190kDa MRP1 protein in membranes of HeLa-T5 cells was inhibited by substrates of MRP1 such as leukotriene C(4), vincrisine, and doxorubicin and by the inhibitor, MK571. LY475776 did not photolabel human MRP2 (ABCC2), MRP3 (ABCC3), MRP5 (ABCC5) or breast cancer resistance protein (ABCG2). Because LY475776 photolabels murine mrp1 less well than human MRP1 and binds to a region believed important for anthracycline binding, studies were conducted with monkey and canine MRP1 which also show a reduced ability to confer resistance to anthracyclines. Unlike murine mrp1, both orthologs were photolabeled well by LY475776. These studies indicate that the specificity of LY475776 is fairly limited to Pgp and MRP1 and further studies will help to define the binding regions.     

Synthesis and biological evaluation of novel membrane-permeant cyclic ADP-ribose mimics: N1-[(5''-O-phosphorylethoxy)methyl]-5'-O-phosphorylinosine 5',5''-cyclicpyrophosphate (cIDPRE) and 8-substituted derivatives

N1-[(5' '-O-Phosphorylethoxy)methyl]-5'-O-phosphorylinosine 5',5'-cyclicpyrophosphate (cIDPRE 2a) and the 8-substituted derivatives 8-bromo-, 8-azido-, 8-amino-, and 8-Cl-cIDPRE (2b-e) were synthesized from N1-[(5'-acetoxyethoxy)methyl]-2',3'-O-isopropylideneinosine (5) in good yields. The pharmacological activities of cIDPRE and the 8-substituted derivatives (2a-e) were analyzed in intact and permeabilized human Jurkat T-lymphocytes. The results indicate that cIDPRE permeates the plasma membrane, releases Ca2+ from an intracellular, cADPR-sensitive Ca2+ store, and subsequently initiates Ca2+ release-activated Ca2+ entry. The Ca(2+)-releasing activity of cIDPRE was confirmed directly in permeabilized cells. Using time-resolved confocal Ca2+ imaging at the single cell level, the development of global Ca2+ signals starting from local small Ca2+ signals evoked by cIDPRE was observed. 8-N3-cIDPRE 2c and 8-NH2-cIDPRE 2d were similarly effective in their agonistic activity as compared to cIDPRE 2a, showing almost indistinguishable concentration-response curves for 2a, 2c, and 2d and very similar kinetics of Ca2+ signaling. In contrast, the halogenated derivatives 8-Br- and 8-Cl-cIDPRE (2b and 2e) did not significantly elevate [Ca2+]i. Therefore, cIDPRE 2a, 8-N3-cIDPRE 2c, and 8-NH2-cIDPRE 2d are novel membrane permeant cADPR mimic and may provide important novel tools to study cADPR-mediated Ca2+ signaling in intact cells.     

Design, synthesis, and evaluation of 3,4-dihydro-2H-[1,4]diazepino[6,7,1-hi]indol-1-ones as inhibitors of poly(ADP-ribose) polymerase

The design, synthesis, and biological evaluation of potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) are reported. A novel series of 3,4-dihydro-2H-[1,4]diazepino[6,7,1-hi]indol-1-ones were designed using a combination of protein structure-based drug design, molecular modeling, and structure-activity relationships (SAR). These novel submicromolar inhibitors possess a tricyclic ring system conformationally restricting the benzamide in the preferred cis orientation. The compounds were designed to optimize space-filling and atomic interactions within the NAD+ binding site of PARP-1. Previously described and newly adapted methods were applied to syntheses of these tricyclic inhibitors. Various modifications were made to the diazepinoindolones at the 6- and 7-positions in order to study this region of the active site and optimize noncovalent interactions. The electron density of derivative 28 bound to chicken PARP-1 revealed that the oxime makes a tight hydrogen bond with the catalytic gamma-carboxylate of glutamic acid (Glu) 988 in accordance with our original designs and models. Most of the compounds have been evaluated for inhibition of human PARP-1. Selected inhibitors were also tested for the ability to potentiate the cytotoxic effect of the DNA-damaging agent Topotecan.