METHODOLOGY/PRINCIPAL FINDINGS: Sprague Dawley rats were separated into 7 groups. Groups 1-2 were orally challenged with carboxymethylcellulose (CMC); group 3 received 20 mg/kg omeprazole and groups 4-7 received 50, 100, 200 and 400 mg/kg of ethanolic leaf extract, respectively. After 1 h, CMC or absolute ethanol was given orally to groups 2-7. The rats were sacrificed after 1 h. Then, the injuries to the gastric mucosa were estimated through assessment of the gastric wall mucus, the gross appearance of ulcer areas, histology, immunohistochemistry and enzymatic assays. Group 2 exhibited significant mucosal injuries, with reduced gastric wall mucus and severe damage to the gastric mucosa, whereas reductions in mucosal injury were observed for groups 4-7. Groups 3-7 demonstrated a reversal in the decrease in Periodic acid-Schiff (PAS) staining induced by ethanol. No symptoms of toxicity or death were observed during the acute toxicity tests.
CONCLUSION: Treatment with the extract led to the upregulation of heat-shock protein 70 (HSP70) and the downregulation of the pro-apoptotic protein BAX. Significant increases in the levels of the antioxidant defense enzymes glutathione (GSH) and superoxide dismutase (SOD) in the gastric mucosal homogenate were observed, whereas that of a lipid peroxidation marker (MDA) was significantly decreased. Significance was defined as p<0.05 compared to the ulcer control group (Group 2).
METHODOLOGY/PRINCIPAL FINDING: Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes.
CONCLUSION/SIGNIFICANCE: The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.
METHODOLOGY/PRINCIPAL FINDINGS: Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4-7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2-7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE(2)) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4-7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4-7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound.
CONCLUSIONS/SIGNIFICANCE: The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE(2) synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein.
METHOD: A cross-sectional study was carried out among Malaysian women in Kuala Lumpur. A total of 362 unmarried women, nulliparous and aged between 18 and 25 years old, were included in this study. Participants were conveniently recruited through online platforms as well as face to face using a self-administered questionnaire with five sections consisting of demographics, menstrual characteristics, Working ability, Location, Intensity, Days of pain, Dysmenorrhea (WaLIDD) score for diagnosing and assessing the severity of dysmenorrhea as well as an evaluation of respondents' general knowledge and practices towards dysmenorrhea. The collected data were analysed using the SPSS tool, a descriptive statistic was used to report demographic characteristics. Inferential statistics was used to report the differentiation, association, and correlations of the variables.
RESULTS: The prevalence of primary dysmenorrhea was 73.2%. It was found that the majority of the respondents had poor knowledge (60%) and poor practices (61.88%) of dysmenorrhea. The most common preventive practices among the respondents were using dietary supplements, and herbs, taking a rest and exercising. The findings also indicated that dysmenorrhea among the respondents was significantly associated with family history of dysmenorrhea (p = 0.002), monthly income (p = 0.001), and knowledge level (p = 0.001).
CONCLUSION: Dysmenorrhea has a high prevalence among women in Malaysia in Kula Lumpur driven by low knowledge and lack of evidence-based practices among these women. Thus, it is critical for Government and healthcare authorities to promote education related to women health among Malaysian women.
METHODS: Cross-sectional survey design was used for the present study. Pricing data from ten counties including one from South-East Asia, two from Western Pacific and seven from Eastern Mediterranean regions were used in this study. Purchasing power parity (PPP)-adjusted mean unit prices for 26 anti-cancer drug presentations (similar pharmaceutical form, strength, and pack size) were used to compare prices of anti-cancer drugs across three regions. A structured form was used to extract relevant data. Data were entered and analysed using Microsoft Excel®.
RESULTS: Overall, Taiwan had the lowest mean unit prices while Oman had the highest prices. Six (23.1%) and nine (34.6%) drug presentations had a mean unit price below US$100 and between US$100 and US$500 respectively. Eight drug presentations (30.7%) had a mean unit price of more than US$1000 including cabazitaxel with a mean unit price of $17,304.9/vial. There was a direct relationship between income category of the countries and their mean unit price; low-income countries had lower mean unit prices. The average PPP-adjusted unit prices for countries based on their income level were as follows: low middle-income countries (LMICs): US$814.07; high middle income countries (HMICs): US$1150.63; and high income countries (HICs): US$1148.19.
CONCLUSIONS: There is a great variation in pricing of anticancer drugs in selected countires and within their respective regions. These findings will allow policy makers to compare prices of anti-cancer agents with neighbouring countries and develop policies to ensure accessibility and affordability of anti-cancer drugs.
METHODS: Four electronic databases including Embase, Medline (via Ovid), Scopus and Google Scholar were searched from inception until October 2019 to identify the studies reporting fentanyl related deaths. Two independent reviewers screened and selected the titles and then evaluated the full texts. Only case studies and case series were included. A structured data extraction tool was used to extract data on the number of deaths, routes of administration, concomitant drug use and toxicological data. The Joanna Briggs Institute quality assessment tool was used to evaluate the quality of included studies. Data were synthesized narratively.
RESULTS: Of 1251 articles identified during initial search, 8 case reports and 9 case series met the inclusion criteria. A total of 1969 deaths were reported in the included studies. Deaths were concentrated in the north American region (n = 1946) and the Nordic region (n = 22). Reported causes of death included fentanyl overdose (n = 321, 56.4%), mixed drug toxicity (n = 196, 34.5%), natural (n = 28, 4.9%), other drug toxicity (n = 10, 1.8%), fentanyl and ethanol intoxication (n = 8, 1.4%), incidental (n = 5, <1%) and aspiration (n = 1). Most common routes of use were intravenous (70.5%) and transdermal routes (23.0%). Deaths came swiftly via the intravenous route. Mean level of blood fentanyl amongst all reported deaths was 0.024 µg/mL.
CONCLUSION: Literature related to fentanyl-associated deaths predominantly come from North America. Deaths are comparatively lower or not reported in peer-reviewed publications from the rest of the world. Abuse through intravenous administration, mixed drug toxicities and self-treatment of breakthrough pain are mainly responsible for majority of the reported deaths.