In vitro screening of topical formulation excipients for epithelial toxicity in cancerous and non-cancerous cell lines.

Chemical excipients used in topical formulations may be toxic to living skin cells. Here, we compared the in vitro toxicity of some common solubilizing excipients against human melanoma cells, human keratinocytes (HaCaT) and primary skin fibroblasts (FB) as examples of cancerous, immortalized and primary human skin cells, often used as experimental models representative of in vivo conditions. Two distinct endpoint assays (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet (CV)) were used. The mechanism of cell death after excipient exposure was assessed through Reactive Oxygen Species (ROS) production, cell membrane integrity and cell cycle progression. Results showed that the surfactants, Labrasol®, Labrafil® and Transcutol®, were less toxic than Triton X-100 (a model irritant) in all cell types whereas the oil, Labrafac®, was non-toxic. The human melanoma WM164 cell line showed the greatest sensitivity toward cytotoxicity after chemical exposure, while the other cell lines were more resistant. The relative excipient cytotoxicity responses observed in the MTT and CV assays were comparable and similar trends were seen in their estimated 50 % inhibitory concentration (IC50) values. DNA fragmentation by flow cytometry after exposing the cells to IC50 concentrations of the excipients showed negligible apoptotic populations. ROS production was increased in all cell types after toxic exposure; however, ROS elevation did not lead to apoptosis. The toxicity profiles of each excipient are not only relevant to their use in formulating safe topical products but also in the potential synergistic efficacy in the topical treatment of melanoma.

Changes in the water quality conditions of Kuwait's marine waters: Long term impacts of nutrient enrichment.

This work analyses a 30 year water quality data set collated from chemical analyses of Kuwait's marine waters. Spatial patterns across six sites in Kuwait Bay and seven sites located in the Arabian Gulf are explored and discussed in terms of the changing influences associated with point and diffuse sources. Statistical modelling demonstrated significant increases for dissolved nutrients over the time period. Kuwait marine waters have been subject to inputs from urban development, untreated sewage discharges and decreasing river flow from the Shatt al-Arab River. Chlorophyll biomass showed a small but significant reduction; the high sewage content of the coastal waters from sewage discharges likely favouring the presence of smaller phytoplankton taxa. This detailed assessment of temporal data of the impacts of sewage inputs into Kuwait's coastal waters establishes an important baseline permitting future assessments to be made as sewage is upgraded, and the river continues to be extracted upstream.

Microbial water quality and sedimentary faecal sterols as markers of sewage contamination in Kuwait.

Microbial water quality and concentrations of faecal sterols in sediment have been used to assess the degree of sewage contamination in Kuwait's marine environment. A review of microbial (faecal coliform, faecal streptococci and Escherichia coli) water quality data identified temporal and spatial sources of pollution around the coastline. Results indicated that bacterial counts regularly breach regional water quality guidelines. Sediments collected from a total of 29 sites contained detectable levels of coprostanol with values ranging from 29 to 2420 ng g(-1) (dry weight). Hot spots based on faecal sterol sediment contamination were identified in Doha Bay and Sulaibikhat Bay, which are both smaller embayments of Kuwait Bay. The ratio of epicoprostanol/coprostanol indicates that a proportion of the contamination was from raw or partially treated sewage. Sewage pollution in these areas are thought to result from illegal connections and discharges from storm drains, such as that sited at Al-Ghazali.

Prevalence of menopausal related symptoms and their impact on quality of life among Egyptian women.

OBJECTIVE: To assess the prevalence of menopausal-related symptoms and to evaluate their impact on quality of life (QoL) among a sample of menopausal women from Egypt. MATERIALS AND METHODS: A cross-sectional hospital-based study conducted at the Gynecology department, Suez Canal University, Ismailia - Egypt. A total 1,214 women aged 40 - 70 years were recruited and studied using an interview questionnaire. The questionnaire contains four main items: socio-demographic data, menstruation status assessment, modified Menopausal Rating Scale (MRS), and World Health Organization Quality of Life (WHOQOL-BREF) questionnaire. RESULTS: Mean age was 48.1 ± 10.3 years, with 26.6% of the studied participants were illiterates. According to menstruation status, 40.9% of the studied women were postmenopausal, 41.4% were premenopausal, while 17.7% were perimenopausal. Most of the studied participants have mild/moderate somatic symptoms. Mild/moderate depressive mode, irritability, and anxiety have been reported in 63%, 58.4%, and 58.2% of women, respectively. Postmenopausal women have significantly higher scores on MRS except for urogenital score that was higher in perimenopausal women. They also had significantly lower QoL score in all subscales of WHOQOL-BREF except for psychological domain that was lowest among perimenopausal women. MRS total score has significant negative correlation to all domains of WHOQOL questionnaire. CONCLUSION: Postmenopausal women have higher prevalence of menopausal symptoms that significantly affect their quality of life more than pre- and perimenopausal women. Those in the transition period (perimenopausal) have higher prevalence of psychological symptoms with higher impact on their psychological welfare.

Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

AIMS: To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. MATERIALS AND METHODS: After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. RESULTS: Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. CONCLUSION: Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

The normal human myometrium has a vascular spatial gradient absent in small fibroids.

BACKGROUND: The human uterine vasculature is highly structured, exhibiting circumferential and radial branching. Previously published angiograms of the arterial network describe a system of regular coils. Uterine fibroids lack this structured vasculature. In this study, we make a comparison between the vasculature in normal myometrium and in fibroids using robust stereological methods thus far lacking in the literature. METHODS: Stereological and morphometric analysis of the vascular system was carried out on 15 normal and 27 small fibroid (5-40 mm) uteri taken from women suffering menorrhagia. Projected images of published angiograms were also re-examined, measuring tortuosity. RESULTS: A decreasing gradient of vascular smooth muscle from outer to inner myometrium was found in normal uteri, with no corresponding gradient in capillary tissue fraction. An association between vascular luminal size, amplitude and frequency of vessel bending was also established. Conversely, fibroids were found to lack structured or muscularized vasculature. CONCLUSIONS: A quantitative gradient within the myometrial vascular system, which is absent in fibroids, has been demonstrated. These structural differences between diseased and healthy tissues are probably because of differing expression of angiogenic growth factors and may explain the distribution of particles seen after uterine artery embolization.

Adrenomedullin limits reperfusion injury in experimental myocardial infarction.

Adrenomedullin (AM) is a vascular-derived polypeptide that exerts numerous actions in cardiovascular homeostasis. Recent studies have demonstrated a cytoprotective action of exogenously applied or genetically over-expressed AM in experimental myocardial infarction. The present studies were undertaken to test the hypothesis that AM exerts its effects through direct augmentation of NO generation in the myocardium during early reperfusion. Rat isolated hearts underwent 35 min left coronary artery occlusion followed by 120 min reperfusion. Infarct size (as percentage of ischaemic riskzone) was determined by Evans' blue and tetrazolium double staining. AM 1 nM administered 5 min prior to and during the first 15 min of ischaemia did not significantly influence infarct size. However, the same concentration of AM given during the last 5 min ischaemia and first 15 min of reperfusion significantly limited infarct size (AM reperfusion 15.9 +/- 3.5% vs control 31.4 +/- 2.1%, P < 0.01). AM at reperfusion improved coronary flow and LV contractility. The protective effects of adrenomedullin were abolished in the presence of the NO synthase inhibitor, L-NAME 100 microM (infarct size 24.6 +/- 5.7%, P > 0.05 vs control). AM treatment at reperfusion was associated with augmented phosphorylation of the pro-survival kinase, Akt, determined by immunoblotting of tissue sampled 30 min following reperfusion. These studies provide the first evidence that AM exerts its cytoprotective action specifically during early reperfusion through a NO-dependent mechanism.

Analysis of Disability Adjusted Life Years (DALYs) among arsenic victims: a cross-sectional study on health economics perspective.

Arsenic contamination of ground water is a major public health problem in Bangladesh. It is estimated that more than 20 million people are potentially exposed to arsenic poisoning. This cross-sectional study was carried out in Haziganj Upazila under Chandpur district between September to December, 2001 with the objectives to assess the socioeconomic consequences and disease burden in terms of Disability Adjusted Life Years (DALYs). A total of 168 subjects suffering from arsenicosis were studied. Both age and disability weights were considered to calculate DALYs. Agricultural labour and housewives suffered more from the disease. A strong relationship (p<0.005) was found between duration of suffering and occupation of the subjects. Also, there was a strong relationship between age of onset and education of the study subjects (p<0.006). No deaths directly from arsenicosis were reported. It may be noticed that 47% of the patients would be living with disability for more than 51 years. A strong relationship exists (p<0.002) between educational level and Years Lived with Disability (YLDs). A total of 7930 YLDs were lost due to arsenicosis, which accounts for 1908 DALYs.

Bisacodyl and high-amplitude-propagating colonic contractions in children.

BACKGROUND: The purpose of these studies was to determine the suitability of bisacodyl for stimulating high-amplitude-propagating contractions in pediatric studies of colonic manometry. METHODS: Water-perfused manometry catheters were inserted into the right colon of children referred for evaluations related to defecation disorders. Colonic motility was measured in a 3-hour test session: an hour fasting, an hour after a meal, and 30 minutes after administration of a provocative agent. RESULTS: Bisacodyl was superior to edrophonium as a stimulant for inducing high-amplitude-propagating contractions. Bisacodyl-induced high-amplitude-propagating contractions were similar in amplitude, duration, propagation velocity, and sites of origin and extinction to naturally occurring high-amplitude-propagating contractions. The effect of intrarectal bisacodyl was similar to that of intracecal bisacodyl, except for a delay of 10 minutes in onset. Bisacodyl induced high-amplitude-propagating contractions in all 28 children (22 with spontaneous high-amplitude-propagating contractions) without evidence of neuromuscular disease and in 2 of 9 children with a colonic neuromuscular disorder and no spontaneous high-amplitude-propagating contractions. CONCLUSIONS: Bisacodyl-induced high-amplitude-propagating contractions were quantitatively and qualitatively similar to naturally occurring high-amplitude-propagating contractions. In selected cases, such as in children receiving total parenteral nutrition or restricted fluid intake, it may be possible to shorten diagnostic colonic manometry using bisacodyl rather than waiting for spontaneous high-amplitude-propagating contractions.