Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma.

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX-SIM-Solution) or nanoemulsions (NEs) (DOX-SIM-NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX-SIM-Solution group (265.30) that was double the %ILS of the DOX-SIM-NE group (134.70). However, DOX-SIM-NE had a non-toxic effect on the haematological parameters, whereas DOX-SIM-Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX-SIM-Solution. A reduction in the side effects of DOX-SIM-NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX-SIM-NE treatment than with the DOX-SIM-Solution treatment. The study showed that incorporating SIM into the DOX-loaded-NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.

Mixed methods evaluation explains bypassing of vouchers in micronutrient powder trial in Mozambique.

Micronutrient powders (MNP) are recommended by the World Health Organization as an effective intervention to address anaemia in children. A formative process evaluation was conducted to assess the viability of a model using free vouchers in two districts of Mozambique to deliver MNP and motivate adherence to recommendations regarding its use. The evaluation consisted of (a) an examination of programme outcomes using a cross-sectional survey among caregivers of children 6-23 months (n = 1,028) and (b) an ethnographic study to investigate delivery experiences and MNP use from caregiver perspectives (n = 59), programme managers (n = 17), and programme implementers (n = 168). Using a mixed methods approach allowed exploration of unexpected programme outcomes and triangulation of findings. The survey revealed that receiving a voucher was the main implementation bottleneck. Although few caregivers received vouchers (11.5%, CI [9.7, 13.6]), one-fourth received MNP by bypassing the voucher system (26.3%, CI [23.6, 29.0]). Caregivers' narratives indicated that caregivers were motivated to redeem vouchers but encountered obstacles, including not knowing where or how to redeem them or finding MNP were not available at the shop. Observing these challenges, many programme implementers redeemed vouchers and distributed MNP to caregivers. Virtually, all caregivers who received MNP reported ever feeding it to their child. This study's findings are consistent with other studies across a range of contexts suggesting that although programmes are generally effective in motivating initial use, more attention is required to improve access to MNP and support continued use.

Matrilysin expression related to radiation and microflora changes in murine bowel.

BACKGROUND: Matrilysin (MMP-7) elevation after radiotherapy is shown in humans. Matrilysin regulates certain cytokines and the production of bactericidal proteins when the mucosa is exposed to bacterial antigens. We investigate the effect of irradiation on matrilysin and microflora in murine bowel, after modulation with antibiotics. METHODS: Animals were divided into two different groups a radiation group (72 animals) and sham radiation group (36 animals). Animals were divided into smaller groups of six according to radiation dose (19 or 38 Gy or sham). Seven days before radiotherapy ampicillin 500 mg/kg/d was administered intramuscularly, in the antibiotic groups. An exteriorized segment of ileum was subjected to single high dose radiation (19 or 38 Gy). Samples were collected 2, 24, and 48 h and analyzed for microflora, MIP-2, TGF-ß, and MMP-7. RESULTS: The combination of antibiotics and irradiation leads to an early significant reduction of bacteria, down-regulates MIP-2, up-regulates TGF-ß and elevation of MMP-7 to levels achieved by antibiotics or irradiation alone. Lactobacilli were reduced to non-existent levels after antibiotics. CONCLUSIONS: Pretreatment with Ampicillin before irradiation and laparotomy in a murine model leads to Matrilysin over-expression as achieved by radiotherapy alone. Microfloral regulation does not affect MMP-7 stimulation after surgical or radiological trauma. Radiotherapy overrides the effect of antibiotics leading to an up-regulation of MMP-7, TGF-ß and MIP-2 expression between 24 h and 48 h.

Serum visfatin concentration and its relationship with sex hormones in obese Saudi women.

Objective: Visfatin is an adipokine secreted mainly by adipose tissue and has been implicated in obesity. It also mimics the effects of insulin and its expression is hormonally regulated by hormones. Serum visfatin concentrations were evaluated in Saudi women of different body weights to determine its relationships with sex hormones and obesity-induced insulin resistance (IR) in women in Saudi Arabia. Methods: In this cross-sectional study, 83 healthy Saudi women of different body weights were recruited between 2014 and 2016, from King Abdulaziz University staff and students. They were divided into three groups according to their body mass indexes (BMIs). Anthropometric measurements were recorded for all of the participants. Blood samples were collected to assess the biochemical variables, including glucose, insulin, lipid profile, visfatin, sex hormone-binding globulin (SHBG), and sex hormones levels. Results: Obese women exhibited significantly higher blood pressure (BP), glucose, insulin, IR, lipid profile, and visfatin levels than overweight and lean women. However, lean women had significantly higher high-density lipoprotein-cholesterol (HDL)-C, estradiol (E2), luteinizing hormone (LH), and SHBG levels than overweight and obese women. Positive correlations were observed between visfatin levels and waist and hip circumferences, BMI, diastolic BP, systolic BP (SBP) insulin, IR, and LDL-C levels (P < 0.001 - P < 0.05). Negative correlations were observed between visfatin levels and HDL-C, SHBG, LH, and E2 levels (P < 0.001 - P < 0.05). Conclusions: The results of this study revealed that E2 and SHBG concentrations were decreased in obese women, while visfatin levels were increased in obese women with high IR levels. This suggests that visfatin levels and sex hormones interact synergistically with obesity with regard to the IR risk in obese women.

Ensuring the supply of and creating demand for a biofortified crop with a visible trait: lessons learned from the introduction of orange-fleshed sweet potato in drought-prone areas of Mozambique.

BACKGROUND: Orange-fleshed sweet potato (OFSP) is a promising biofortified crop for sub-Saharan Africa because it has high levels of provitamin A carotenoids, the formed vitamin A is bioavailable, and white-fleshed sweet potato is already widely grown. OBJECTIVES: To examine whether farmers will adopt varieties with a distinct visible trait, young children will eat OFSP in sufficient quantities to improve vitamin A intake, OFSP can serve as an entry point for promoting a more diversified diet, and lessons can be drawn to assure sustained adoption. METHODS: The 2-year quasi-experimental intervention study followed households and children (n = 741; mean age, 13 months at baseline) through two agricultural cycles in drought prone-areas of Mozambique. RESULTS: OFSP is acceptable to farmers when introduced by using an integrated approach. In the second year, intervention children (n = 498) were more likely than control children (n = 243) to have consumed OFSP (54% vs. 4%), dark-green leaves (60% vs. 46%), or ripe papaya (65% vs. 42%) on 3 or more days in the previous week (p < .001 for all comparisons). Their vitamin A intakes were nearly eight times higher than those of control children (median, 426 vs. 56 1g RAE [retinol activity equivalents], p < .001). Diet diversification was limited by difficult agroecological conditions and low purchasing power. However, dietary diversity was higher among intervention than control children (32% vs. 9% consuming food from more than four groups; p < .001). CONCLUSIONS: An integrated OFSP-based approach had a positive impact on the vitamin A intake of young children. A market development component and improved vine multiplication systems are recommended to assure sustained adoption.

Bifidobacterium infantis strains with and without a combination of oligofructose and inulin (OFI) attenuate inflammation in DSS-induced colitis in rats.

BACKGROUND: Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. METHODS: Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1beta, TNF-alpha, IL-10 and TGF-beta) and malondialdehyde (MDA). RESULTS: OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1beta decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. CONCLUSION: Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations.

Studies on the molluscicidal activity of Agave angustifolia and Pittosporum tobira on schistosomiasis transmitting snails.

In the search for new molluscicidal plants for controlling the snail vectors of schistosomiasis, laboratory evaluation was made to assess the molluscicidal activity of Agave angustifolia and Pittosporum tobira plants against Biomphalaria alexandrina snails. Results indicated that both plants have promising molluscicidal activity as the LC90 of the dry powder of both plants was 120 ppm. Both plants showed marked cercaricidal and miracidicidal potencies against S. mansoni larvae. The LC90 of both plants (120 ppm) killed most B. alexandrina eggs within 24 h of exposure. The sub-lethal concentrations of both plants markedly suppressed the survival rate of B. alexandrina snails and the mortality increased with increasing the concentrations and the exposure period up to 10 successive weeks. The accumulative toxic effect of these concentrations was continuous during the recovery period. Also, the reproductive rates of exposed snails were greatly affected even through the recovery period. This depression in reproductive ability of snails was accompanied by histological damage in the hermaphrodite glands of exposed snails. Meanwhile, the growth of snails was estimated weekly and it showed great inhibition in exposed snails comparing with the control ones.

Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model.

BACKGROUND: Leucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy. METHOD: A midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion) were then analysed in ileal venules 2 - 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO) and cell histology were analysed. RESULTS: The highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation. CONCLUSION: This study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological recruitment of leucocytes and changes in intestinal microflora in the small bowel after radiotherapy.

Feeding spinach thylakoids to rats modulates the gut microbiota, decreases food intake and affects the insulin response.

Thylakoid membranes derived from green leaf chloroplasts affect appetite-regulating hormones, suppress food intake, reduce blood lipids and lead to a decreased body weight in animals and human subjects. Thylakoids also decrease the intestinal in vitro uptake of methyl-glucose in the rat. The aim of this study was to investigate the effect of dietary thylakoids on the gut microbiota composition, mainly the taxa of lactobacilli and bifidobacteria, in rats fed either a thylakoid-enriched diet or a control diet for 10 d. At the same time, a glucose-tolerance test in the same rats was also performed. Food intake was significantly decreased in the thylakoid-fed rats compared with the control-fed rats over the 10-d study. An oral glucose tolerance test after 10 d of thylakoid- or control-food intake resulted in significantly reduced plasma insulin levels in the thylakoid-fed rats compared with the control-fed rats, while no difference was observed for blood glucose levels. Analysis of gut bacteria showed a significant increase of lactobacilli on the ileal mucosa, specifically Lactobacillus reuteri, in the rats fed the thylakoid diet compared with rats fed the control diet, while faecal lactobacilli decreased. No difference in bifidobacteria between the thylakoid and control groups was found. Analyses with terminal restriction fragment length polymorphism and principal component analysis of faeces demonstrated different microbial populations in the thylakoid- and control-fed animals. These findings indicate that thylakoids modulate the gut microbial composition, which might be important for the regulation of body weight and energy metabolism.

Structural determinants of adolescent girls' vulnerability to HIV: views from community members in Botswana, Malawi, and Mozambique.

In sub-Saharan Africa, adolescent girls are three to four times more likely than adolescent boys to be living with HIV/AIDS. A literature review revealed only four studies that had examined HIV vulnerability from the perspective of community members. None of the studies focused specifically on adolescent girls. To fill this gap, in 2008 12 focus group discussions were held in selected peri-urban and rural sites in Botswana, 12 in Malawi, and 11 in Mozambique to identify factors that render girls vulnerable to HIV infection from the community members' perspective. The preponderance of comments identified structural factors--insufficient economic, educational, socio-cultural, and legal support for adolescent girls--as the root causes of girls' vulnerability to HIV through exposure to unprotected sexual relationships, primarily relationships that are transactional and age-disparate. Community members explicitly called for policies and interventions to strengthen cultural, economic, educational, and legal structures to protect girls, recognized community members' responsibility to take action, and requested programs to enhance adult-child communication, thus revealing an understanding that girls' vulnerability is multi-level and multi-faceted, so must be addressed through a comprehensive approach to HIV prevention.

Therapy related CMML: a case report and review of the literature.

Therapy related chronic myelomonocytic leukemia (t-CMML) is rare. We report a 23-year-old female who developed acute fulminant hepatic failure after drug overdose. She underwent ABO incompatible orthotopic liver transplant. She received cyclophosphamide along with other immunosuppressants. Seven years later, she was diagnosed with t-CMML-2 with 45XX,-7 karyotype. She received 4 cycles of azacitidine and proceeded with allogeneic bone marrow transplant. This is the first a case of t-CMML reported in a liver transplant recipient. In this article, we also summarize all reported cases of t-CMML, and we review therapy related MDS in recipients of solid organ transplant.

Probiotics and blueberry attenuate the severity of dextran sulfate sodium (DSS)-induced colitis.

We studied the anti-inflammatory properties of probiotic strains and blueberry in a colitis model. The disease activity index (DAI) was significantly lower on days 9 and 10 in all groups compared to the colitis control. Myeloperoxidase (MPO) and bacterial translocation to the liver and to the mesenteric lymph nodes (MLN) decreased significantly in all groups compared to colitis control. Cecal Enterobacteriaceae count decreased significantly in blueberry with and without probiotics compared to the other groups. Lactobacillus plantarum reisolated from the cecal content in the presence of blueberry, contrary to Lactobacillus fermentum. Colonic MDA decreased significantly in all groups, except the L. fermentum group, compared to the colitis control. The cecal concentration of acetic, propionic, and butyricbutyric acid was significantly higher in the L. plantarum group, while the L. fermentum group yielded the highest concentration of lactic acid compared with all other groups. Lactobacillus plantarum DSM 15313, Lactobacillus fermentum 35D, and blueberry alone and in combination improve the DAI, reduce bacterial translocation, and reduce inflammation.

Susceptibility of Sudanese Nubian goats, Nilotic dwarf goats and Garag ewes to experimental infection with a mechanically transmitted Trypanosoma vivax stock.

The present study was conducted to study the susceptibility of two different types of Sudanese goats namely: Black Nubian, the Nilotic dwarf goats and ewes of Garag type to experimental infection with Trypanosoma vivax stock isolated from cattle outside tsetse area. The infection caused parasitaemia, anaemia and pyrexia in the infected goats. However, the Nilotic dwarf goats were more tolerant to the infection than the Nubian goats, showing significantly higher values of packed cell volume, haemoglobin concentration, total red and white blood cells counts and significantly low parasitaemia and low body temperature. Garag ewes which were found to be susceptible to T. vivax infection showed different signs of anaemia and pyrexia; it is recommended that comparative studies on sensitivity of this type and other different Sudanese types of sheep to Trypanosomosis should be conducted.

A food-based approach introducing orange-fleshed sweet potatoes increased vitamin A intake and serum retinol concentrations in young children in rural Mozambique.

Vitamin A deficiency is widespread and has severe consequences for young children in the developing world. Food-based approaches may be an appropriate and sustainable complement to supplementation programs. Orange-fleshed sweet potato (OFSP) is rich in beta-carotene and is well accepted by young children. In an extremely resource poor area in Mozambique, the effectiveness of introduction of OFSP was assessed in an integrated agriculture and nutrition intervention, which aimed to increase vitamin A intake and serum retinol concentrations in young children. The 2-y quasi-experimental intervention study followed households and children (n = 741; mean age 13 mo at baseline) through 2 agricultural cycles. In y 2, 90% of intervention households produced OFSP, and mean OFSP plot size in intervention areas increased from 33 to 359 m(2). Intervention children (n = 498) were more likely than control children (n = 243) to eat OFSP 3 or more d in the last wk (55% vs. 8%, P < 0.001) and their vitamin A intakes were much higher than those of control children (median 426 vs. 56 microg retinol activity equivalent, P < 0.001). Controlling for infection/inflammation and other confounders, mean serum retinol increased by 0.100 micromol/L (SEM 0.024; P < 0.001) in intervention children and did not increase significantly in control subjects. Integrated promotion of OFSP can complement other approaches and contribute to increases in vitamin A intake and serum retinol concentrations in young children in rural Mozambique and similar areas in Sub-Saharan Africa.

Modulation of the effect of dextran sulfate sodium-induced acute colitis by the administration of different probiotic strains of Lactobacillus and Bifidobacterium.

The pathogenic mechanism of inflammatory bowel diseases is not fully understood but colonic microflora including Lactobacillus and Bifidobacterium species may affect the induction of colonic inflammation. In this study the relative efficacy of different probiotic organisms in the prevention of colitis was compared in an induced rat colitis model. Three Lactobacillus strains and two Bifidobacterium strains were fed to Sprague-Dawley rats for 7 days prior to offering the rats 5% dextran sulfate sodium (DSS) in their drinking water to induce colitis and the administration of the probiotics continued for 7 days with the DSS. Colitis severity was assessed daily using a disease activity index (DAI). Samples were collected 7 days after colitis induction for intestinal bacterial flora and bacterial translocation. The DAI decreased significantly on days 4, 5, 6, and 7 in the Lactobacillus plantarum DSM 9843, Bifidobacterium sp. 3B1, and Bifidobacterium infantis DSM 15158 groups compared to the colitis control. It decreased significantly on days 5, 6, and 7 in the Bifidobacterium infantis DSM 15158 group compared to the Lactobacillus paracaesi DSM 13434 and Lactobacillus gasseri 5B3 groups. It also decreased significantly on day 7 in the L. plantarum DSM 9843 group compared to the L. gasseri 5B3 group. Bacterial translocation to the mesenteric lymph nodes decreased significantly in all treatment groups compared to the colitis control. Enterobacteriaceae bacterial translocation to the liver decreased in all treatment groups compared to the colitis control. Administration of certain strains of Lactobacillus and Bifidobacterium significantly improves the DAI and reduces bacterial translocation, and L. plantarum DSM 9843, Bifidobacterium sp. 3B1, and Bifidobacterium infantis DSM 15158 seem to have the best effect.