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Effects of chronic alcohol abuse on alveolar epithelial barrier function and glutathione homeostasis.

BACKGROUND: An association between the development and severity of the acute respiratory distress syndrome has been described in individuals who abuse alcohol chronically, possibly through a mechanism involving the deficiency of pulmonary glutathione. In a rodent model of chronic alcohol abuse, this antioxidant contributes to the maintenance of alveolar-capillary membrane integrity. We postulated that humans who chronically abuse alcohol will have similar alterations in alveolar-capillary barrier function. METHODS: Bronchoalveolar lavage was performed in 18 healthy chronic alcoholics and 18 control subjects; total protein and glutathione concentrations were measured within the epithelial lining fluid. To examine possible protracted effects of alcohol abuse, a subset of 11 chronic alcoholic subjects underwent a second bronchoalveolar lavage after a week of abstinence. RESULTS: Chronic alcoholic subjects had significantly elevated protein concentrations compared with controls (8.64 microg protein/ng immunoglobulin A vs. 5.91 microg protein/ng immunoglobulin A, p = 0.01). After a week of abstinence, no significant increase in either the glutathione levels or normalization of the protein concentrations in the epithelial lining fluid was demonstrable. CONCLUSIONS: Increased protein levels in the epithelial lining fluid of individuals who abuse alcohol chronically may signify abnormal alveolar epithelial barrier function that does not appear to readily reverse after a period of abstinence.

Adult↗

Glutamine depletion and increased gut permeability in nonanorectic, non-weight-losing tumor-bearing rats.

BACKGROUND & AIMS: Glutamine is an essential amino acid for rapidly dividing cells such as enterocytes. The progress of cancer is associated with a decrease of arterial and muscle glutamine concentrations. The aim of this study was to test whether increasing tumor loads affect gut intracellular glutamine handling, protein turnover, and gut absorptive and barrier function. METHODS: Methylcholantrene-induced tumor-bearing rats were studied with a subcutaneous tumor load of 5%-15% or 15%-30% of body weight. Portal drained visceral net uptake or release of energy substrates, amino acids, and intestinal protein turnover were studied. Gut absorptive capacity and permeability was assessed by the urinary recovery of 3-O-methyl-D-glucose or lactulose-rhamnose ratio after an oral gavage. RESULTS: In tumor-bearing rats, the net uptake of energy substrates (ketones and glutamine) and net protein synthesis increased across the portal drained viscera, whereas mucosal glutamine concentrations decreased. Absorptive capacity remained unchanged in both tumor-bearing groups. However, the lactulose-rhamnose ratio increased with increasing tumor load, indicating loss of gut barrier function. This was not related to changes in villus height, crypt depth, or changes in mucosal cell populations but to decreased intracellular polyamine concentrations. CONCLUSIONS: The presence of a methylcholantrene tumor leads to altered mucosal glutamine metabolism and loss of gut barrier function possibly related to disturbed proliferation or differentiation of enterocytes.

Amino Acids↗

The association between characteristics of dating relationships and condom use among heterosexual young adults.

Although there is some evidence that relationship-level factors influence sexual behavior, they have received far less attention than individual-level factors as potential correlates of condom use. This study surveyed 210 undergraduate men and women to examine the association between relationship characteristics and condom use. Higher levels of love, longer relationships and more serious and committed relationships were individually associated with less condom use. In a multiple logistic regression model controlling for HIV/sexually transmitted disease (STD) risk perception and contraceptive method, relationship length was the only relationship factor that independently predicted condom use (OR = .91; 95% CI = .84-.99). Use of a hormonal contraceptive method was negatively associated with condom use in the multivariate model (OR = .12; 95% CI = .06-.27), and mediated the association between relationship factors and condom use. Study results suggest that HIV/STD prevention interventions may be improved by addressing relationship characteristics, particularly the length of a dating relationship.

Acquired Immunodeficiency Syndrome↗

The value and use of different contraceptive methods.

Reductions in the rates of maternal and child mortality as well as in demographic growth are directly linked to contraceptive usage. The development and availability of safer, improved contraceptives which are convenient to use could be expected to be used by a larger group of individuals and thus make an impact on reproductive health as well as on population growth rates. Such arguments have been used to support contraceptive research. This article deals with some of the developments that have occurred as a consequence of such efforts.

Contraception↗

Dietary glucosylceramide improves skin barrier function in hairless mice.

BACKGROUND: Sphingolipids are known to play an important role in both water retention and epidermal permeability barrier function in mammalian stratum corneum. However, little is known about the effects on epidermal function of orally administered sphingolipids. OBJECTIVE: We examined the effect of dietary glucosylceramide (GluCer) on the maintenance and recovery of epidermal barrier function. METHODS: Hairless mice were fed a particular diet (HR-AD) for 4 weeks to induce chronic skin perturbation. Subsequently, a normal diet supplemented with GluCer (from rice bran and germ) was provided for the next 4 weeks. Transepidermal water loss (TEWL) and stratum corneum flexibility were measured throughout this recovery phase. Additional hairless mice were fed a diet with or without a maize-extracted GluCer supplement for 5 weeks, then their skin was acutely perturbed with repeated tape-stripping, and the TEWL was measured. RESULTS: Although skin functions were generally lower following chronic perturbation, in GluCer-fed mice the TEWL was significantly reduced at 2 weeks and the stratum corneum flexibility was increased at 3 weeks compared to controls. Following acute barrier perturbation by tape-stripping, mice an HR-AD fed a GluCer diet exhibited enhanced recovery compared with the control diet group. CONCLUSION: These results demonstrate that in hairless mice skin barrier functions impaired by chronic or acute perturbations were improved by dietary GluCer. The oral administration of GluCer may be useful for the preservation and recovery of epidermal barrier functions an HR-AD.

Adhesives↗

Lubrication use in condom promotion among commercial sex workers and their clients in Ratchaburi, Thailand.

Condom promotion has been intensified in Thailand to prevent the spread of HIV. A water soluble lubricant (WSL) could be used to alleviate many unpleasant side effects of frequent condom use experienced by sex workers and their clients. This study was conducted to determine the efficacy of WSL use in preventing the side effects of condom use including condom breakage, and to assess the acceptance of WSLs within the sex-worker population. The results of this study showed that 83 (111) of the 134 sex workers reported use of the WSL provided during the study period and more than 95 per cent (106) expressed interest in employing the WSL regularly, saying that WSLs reduce unpleasant side-effects relating to frequent condom use. Also 70 per cent of them reported that the majority of their clients found using the WSL made condom use more enjoyable. A follow-up study showed that 57 per cent of the respondents were still using a WSL on a regular basis and all of them felt it reduced condom breakage. Therefore, WSL use should be an acceptable and useful method for alleviating problems associated with regular use of condoms within the sex-worker population. In addition, there is evidence that WSLs can reduce the incidence of condom breakage. Thus, WSLs could be valuable tools in condom promotion for AIDS control within this high risk population and their clients.

Adolescent↗

Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon.

BACKGROUND/AIMS: Glutamine (Gln) is considered a trophic factor for small intestinal epithelia, which is important during severe illness. Its use in parenteral nutrition is precluded by its instability, a problem that may be overcome by use of the stable dipeptide L-alanyl-L-glutamine (Ala-Gln). The hypothesis was tested that Gln or Ala-Gln may stimulate cell proliferation not only in the ileum but also in the proximal and distal colon and, thus, may contribute to the gut barrier function. METHODS: Biopsy samples from the normal human ileum, proximal colon, and rectosigmoid were incubated for 4 hours with Gln (2 mmol/L), Ala-Gln (2 mmol/L), and saline (control). Cells in S phase were labeled with bromodeoxyuridine. In longitudinal crypt sections labeled and quiescent cells were counted. RESULTS: Gln as well as Ala-Gln stimulated crypt cell proliferation in the ileum, proximal colon, and rectosigmoid colon. In ileal specimens, labeling was greater in the entire crypt, whereas in both colonic regions, the trophic effect was confined to the basal crypt compartments. CONCLUSIONS: Gln and Ala-Gln have trophic effects not only in the ileum, but also in the proximal and distal colon. This could be important during parenteral nutrition when mucosal atrophy may weaken the gut barrier.

Adult↗

The influence of apoptosis on intestinal barrier integrity in rats.

BACKGROUND: Apoptosis is a critical step responsible for maintaining the cellular balance between proliferation and death and for controlling tumorigenesis. Although an increase in intestinal apoptotic cells has been considered to be associated with the pathogenesis of gastrointestinal injury, little is understood concerning the role of apoptosis in the development of intestinal barrier dysfunction. METHODS: Apoptosis induced by intraperitoneal injection of doxorubicin in rats was evaluated by transmission electron microscopy and the TUNEL histochemistry method. Treatment with deoxy-D-glucose (a glycolytic pathway inhibitor) or cycloheximide (a protein synthesis inhibitor) was performed after doxorubicin challenge. Passage of human serum albumin from blood to the intestinal interstitium and the intestinal lumen or from the intestine to the intestinal interstitium and blood was evaluated by means of albumin clearance. RESULTS: A significant increase in gut water content, albumin flux, and bidirectional clearance of albumin accompanied by apoptotic epithelial cell increase was noted in doxorubicin-challenged rats treated with saline. The increase in endothelial and epithelial permeability and the increase of apoptosis could partly be prevented by treatment with deoxy-D-glucose or cycloheximide. CONCLUSION: Doxorubicin-increased epithelial apoptosis within the intestine occurs simultaneously with increased bidirectional permeability of the intestinal barrier, probably associated with both glycolytic and protein synthesis pathways. Apoptosis may thus play a role in the pathogenesis of intestinal barrier dysfunction.

Animals↗

Post-tubal sterilization syndrome--a misnomer.

Menstrual parameters and gynecologic symptoms of 389 women who underwent laparoscopic tubal banding were studied prospectively and longitudinally. Previous oral contraceptive users exhibited an immediate increase in menstrual flow and dysmenorrhea, which declined slightly with time. No such changes occurred in women who used other methods of temporary contraception. A significant increase in noncyclic pelvic pain, independent of previous contraceptive usage, developed only in women greater than 38 years of age. Menstrual cycles and dyspareunia were not affected. A small control group of women whose husbands underwent vasectomy showed no significant changes in any of these parameters.

Adult↗

Heterosexual experiences and partnerships of urban, low-income African-American and Hispanic youth.

We have used data from a probability sample of African-American and Hispanic youth living in low-income urban household to describe their heterosexual experiences and the influence of relationships with different kinds of sexual partners (married/lived with, well known, casual) on types of intercourse (oral, anal, vaginal), condom use, and use of other birth control methods. The Generalized Estimating Equation method for data sets with multiple observations on the same subject was used to examine whether an individual's behavior differs with different kinds of partners and how behavior with a given partner is affected by experience with other relationships. Results indicate that (a) with the exception of African-American men, sexual and contraceptive behavior varied considerably with different kinds of partners; (b) heterosexual oral and anal intercourse is more common among Hispanic than African- American youth; and (c) regardless of experience with other relationships, consistent condom use as well as use of any type of contraceptive method tend to be less likely with a casual sex partner. Data regarding percentages of consistent condom use (20%-45%) and increased involvement in risky behavior associated with multiple partners further emphasize the need for interventions that enhance condom use and discourage involvement with multiple partners.

Adolescent↗

The immune-enhancing enteral agents arginine and glutamine differentially modulate gut barrier function following mesenteric ischemia/reperfusion.

BACKGROUND: Immune-enhancing enteral diets have been shown to improve patient outcome. One contributing mechanism may be via maintenance of gut barrier function. While recent data has shown that glutamine is beneficial, arginine may be harmful. We therefore hypothesized that the immune-enhancing agents, glutamine and arginine, differentially modulate gut barrier function. METHODS: At laparotomy, rats had jejunal sacs filled with 10 mmol/L glutamine, arginine, fructose, or magnesium sulfate (osmotic control) followed by 60 minutes of superior mesenteric artery occlusion and 2 hours of reperfusion. Jejunum was harvested for histology, deconvolution microscopy, F:G actin, ATP, and permeability measurements. RESULTS: Glutamine and fructose minimized mucosal injury compared with controls and arginine. Deconvolution microscopy confirmed that glutamine and fructose preserved the actin cytoskeleton but there was disruption by arginine which correlated with F:G actin ratios and tissue ATP levels. Permeability was enhanced by arginine compared with the other groups. CONCLUSION: Arginine resulted in worsened mucosal injury, disruption of the actin cytoskeleton, decreased tissue ATP and enhanced permeability compared with glutamine which appeared protective. The immune-enhancing agent arginine results in breakdown of gut barrier function which may have important implications for critically injured patients.

Actins↗

The Helicobacter felis mouse model in assessing anti-Helicobacter therapies and gastric mucosal prostaglandin E2 levels.

BACKGROUND: The aims of the present study were to assess the usefulness of the Helicobacter felis mouse model in the evaluation of antimicrobial therapies and the effect of Helicobacter infection on gastric mucosal prostaglandin E2 release. METHODS: Barrier-maintained BALB/c mice were infected with H. felis and treated with different antibacterial therapies. H. felis status was determined by bacterial culture, urease test, and bacterial and histologic stainings. Release of prostaglandin E2 from the gastric mucosa was measured by radioimmunoassay. RESULTS: All triple-treated mice were cleared of bacteria both 24 h and 1 month after treatment. However, tinidazole alone also resulted in 100% eradication. Monotherapies with erythromycin acistrate, tetracycline, colloidal bismuth subcitrate, and nitecapone failed to eradicate the bacteria. The release of gastric prostaglandin E2 was doubled in the infected mice (554 +/- 39, mean +/- SE) compared with the noninfected mice (270 +/- 35) (p < 0.01). CONCLUSIONS: The H. felis mouse model proved satisfactory for assessing both anti-Helicobacter therapies and the prostaglandin E2 release. The reliability of this method was improved when several methods to assess the H. felis status were used in parallel.

Amoxicillin↗

Promoting maternal health through family planning in Nigeria.

In 1987, Nigeria embarked on family health initiative as a matter of policy to improve maternal and child health. The prevalent rate of use of modern method of contraceptives for the whole nation is about 6% whereas the figure for high school teachers in Remo division of Ogun state is 44.8%. High school teachers are respected in the various communities and occupy middle grade socio-economic status. As the link between the youths and the adult population there is a role for them to play in the family health initiative in the country.

Family Planning Services↗

Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood-aqueous barrier breakdown.

PURPOSE: Recent clinical studies show that a single intravitreal injection of the corticosteroid triamcinolone acetonide (TAA) may reduce edematous retinal swelling and improve visual acuity in patients with diabetic macular edema (DME). In addition, clinical and experimental studies strongly suggest that blood-retinal barrier breakdown in diabetes is induced by vascular endothelial growth factor (VEGF). These results suggest that corticosteroids may modulate VEGF-mediated responses in vivo. To test this hypothesis directly, the current study evaluated the effects of TAA and dexamethasone (DEX) in a newly developed rabbit model of VEGF-induced blood-retinal barrier and blood-aqueous (iris) barrier breakdown. METHODS: VEGF165 or vehicle was injected intravitreally in female Dutch Belt rabbits, and scanning ocular fluorophotometry was used to non-invasively measure fluorescein leakage from retinal and iris vasculature. VEGF-induced retinal vasculopathy was further assessed with fundus imaging, fluorescein angiography, and ocular coherence tomography. For pharmacologic studies, rabbits were treated with either DEX (2 mg kg(-1) daily, s.c.), TAA (2 or 4 mg, intravitreal), indomethacin (20 mg kg(-1) daily, s.c.), or vehicle (s.c. or intravitreal). Human umbilical vein endothelial cells (HUVEC) were loaded with the fluorescent Ca2+ indicator dye fluo-4 and treated with dexamethasone (0.1-10 microM) or vehicle for either 2 or 24 hr prior to stimulation with 10 ng ml(-1) VEGF165. RESULTS: VEGF injected intravitreally induced a time and dose-dependent breakdown of the blood-retinal and blood-aqueous barriers. Maximal vascular leakage was measured at 48 hr after intravitreal injection with a dose of 500 ng VEGF. Other effects of VEGF included prominent retinal vasodilation, vessel tortuousity, fluorescein leakage from retinal vessels, and inner retinal edema. These VEGF-mediated responses are transient and approach baseline by 1 week. VEGF-induced blood-retinal and blood-aqueous barrier breakdown was completely blocked by the corticosteroid DEX administered systemically for 3 days. In contrast, the non-steroidal anti-inflammatory drug, indomethacin, had no effect. In a separate study with VEGF injected intravitreally at six different time points over 5 months, a single intravitreal 2 mg dose of TAA completely blocked VEGF-induced retinal and iris leakage for 45 days. VEGF/VEGF receptor-2-mediated Ca2+ mobilization in endothelial cells was not affected by 2 or 24 hr pretreatment with dexamethasone. CONCLUSION: These results indicate that one mechanism by which corticosteroids block blood-ocular barrier breakdown and edema is via their modulation of signaling or effector proteins downstream of the VEGF receptor.

Animals↗

Effects of age and non-hormonal contraception on menstrual cycle characteristics.

The objective of this study was to investigate the effects of age and non-hormonal contraceptive method on menstrual cycle parameters. The menstrual cycle data were collected prospectively, and the study was cross-sectional with regard to age. The subjects were 142 women, including 14 asymptomatic volunteers and 128 women who presented to a premenstrual tension (PMT) clinic. The age range was 20-45 years. Contraceptive methods used were intrauterine device (IUD) (n = 12), tubal ligation (n = 61) and non-intensive methods (n = 69). Daily menstrual cycle diaries were used to calculate cycle length and number of days of menstruation. Daily 24-h urine collections were used to calculate the day of the preovulatory estrogen peak. Pearson correlations found significant relationships between age and preovulatory estrogen peak day (p < 0.001) and length of cycle (p < 0.002), but not between age and length of menstruation or luteal phase. Analysis of variance was highly significant for age and contraceptive method, for both cycle length and preovulatory estrogen peak day. Non-intrusive contraception users aged 30 years and younger had significantly longer follicular phases than did women with tubal ligation (p < 0.05). It was concluded that cycle length decreases with age due to shortening of the follicular phase. Further research on whether tubal ligation affects ovulation and follicular phase length in young women is needed.

Adult↗

[Clinical effect of treatment for clearing heat, detoxicating and nourishing Yin on patients with glucocorticosteroid induced facial dermatitis and its effect on skin barrier function].

OBJECTIVE: To observe the clinical efficacy of treatment for clearing heat, detoxicating and nourishing Yin (abbr. as CHM) on glucocorticosteroid (GCS) induced facial dermatitis, and its effect in repairing skin barrier function. METHODS: One hundred and fifteen patients were randomly assigned into two groups, 68 in the treated group treated with CHM and 47 in the control group treated by oral administration of loratadine 10 mg once a day and ketotifen 1 mg once every night. The volume of transepidermal water loss (TEWL) of patients was measured before and after treatment. RESULTS: The effective rate was 77.9% (53/68) and 14.9% (7/47) in the treated group and the control group respectively, showing significant difference between the two groups, and it was better in the treated group than that in the control group (P < 0.01). The decrease of TEWL in the treated group was also superior to that in the control group (P < 0.01). CONCLUSION: Chinese herbal treatment for clearing heat, detoxicating and nourishing Yin has significant clinical efficiency on GCS induced facial dermatitis and in repairing the skin barrier function.

Adolescent↗

Resuscitation-induced gut edema and intestinal dysfunction.

BACKGROUND: Mesenteric venous hypertension and subsequent gut edema play a pivotal role in the development of intra-abdominal hypertension. Although gut edema is one cause of intra-abdominal hypertension, its impact on gut function is unknown. The purpose of this study was to create a model of acute hydrostatic gut edema and to evaluate its effect on gut motility and barrier function. METHODS: The first study, group A, evaluated the effect of gut edema on transit over time using 20 mL/kg 0.9% saline. The second study, group B, focused on the 12-hour time period using 80 mL/kg 0.9% saline. Rats were randomized to superior mesenteric vein partial occlusion (venous hypertension) or sham surgery. At 6, 12, and 24 hours, group A underwent intestinal transit and tissue water weight measurements. At 12 hours, group B underwent tissue water, transit, ileal permeability and resistance, lactate and myeloperoxidase activity, and mucosal injury measurements. RESULTS: Venous hypertension with fluid resuscitation caused acute hydrostatic gut edema, delayed intestinal transit, increased mucosal permeability to macromolecules, and decreased tissue resistance over time. Mucosal injury was minimal in mesenteric venous hypertension. CONCLUSION: Acute mesenteric venous hypertension and resuscitation-induced gut edema, in the absence of ischemia/reperfusion injury, is associated with delayed intestinal transit and altered gut barrier function.

Animals↗

Contraception and ectopic pregnancy risk.

Studies of the association of ectopic pregnancy with contraception have generated a conflicting array of results because of methodologic differences between studies. We estimated the absolute incidence rates of ectopic pregnancy for various contraceptives by multiplying the pregnancy rate by the proportion of pregnancies with ectopic implantation for each method. Our results indicated a more than 500-fold difference in ectopic pregnancy incidence, from a low of 0.005 ectopic pregnancies per 1000 women years of oral contraception or vasectomy to a high of 2.6 per 1000 women years of no contraception. These estimated incidence rates should be useful for clinicians and patients seeking to better understand the risks and benefits of contraceptives.

Adult↗