Dietary Lipids and Cancer

For many years, epidemiological studies continued to suggest that high fat diets are linked to an increased incidence of certain cancers. However, whether the oncogenic properties of fat are associated with their quantity rather than the quality has become debatable. Epidemiological studies have been suggesting that n-6 polyunsaturated fatty acids (n-6 PUFA) and saturated fats are more likely to increase the incidence of cancer, whereas monounsaturated fatty acids (MUFA) and n-3 polyunsaturated fatty acids (n-3 PUFA) are more likely to prevent or decrease the chance of carcinogenesis. A firm conclusion cannot be drawn yet because of insufficient research. This paper reviews the current knowledge of the effects of saturated fats, different types of unsaturated fats, and fat-soluble vitamins on the etiology of cancer

Analysis of outcomes of endovascular embolisation: A cross-sectional two-center study on 46 visceral artery pseudoaneurysms.

PURPOSE: Visceral artery pseudoaneurysms (VAPAs) are uncommon in clinical practice but may have serious clinical outcomes up to death. Endovascular management is a safe effective alternative option to traditional surgical procedures. This study assesses the outcome of different embolic materials and techniques used in the endovascular management of VAPAs. MATERIALS AND METHODS: This is a two-center retrospective analysis of endovascular embolisation of 46 VAPAs, with a mean pseudoaneurysm size of 13 ± 11.35 mm, that were urgently managed between July 2018 and March 2020. Patients' presentations were GIT hemorrhage, intrabdominal hemorrhage, hematuria, and abdominal pain in 34.78%, 30.43%, 23.91%, and 10.87% respectively. Management using coils only was done in 28/46 patients (60.87%), NBCA glue only in 16/46 patients (34.78%), combined coils and NBCA glue in 1/46 patient (2.17%), and Amplatzer plugs only in 1 patient (2.17%). The management techniques were sac packing in 9/46 patients (19.57%), inflow occlusion in 28/46 patients (60.87%) and trapping in 9/46 patients (19.57%). All patients were followed-up for 1 year after the procedure. RESULTS: The overall clinical success and periprocedural complication rates were 93.48%, and 15.22% respectively, and 30-day mortality was zero. Clinical success was 92.86% in the coil subgroup (n = 28), and 93.75% in the NBCA glue subgroup (n = 16). The technical success rate was 100%. Effectiveness of the procedures during the follow-up was 97.83%. Target lesion re-intervention rate was 2.17%. CONCLUSION: Transarterial embolisation can provide high technical and clinical success rates with low periprocedural complication and re-intervention rates, as well as satisfactory procedure effectiveness in the management of VAPAs

Male involvement in birth preparedness and complication readiness for emergency obstetric referrals in rural Uganda

<p>Abstract</p> <p>Background</p> <p>Every pregnant woman faces risk of life-threatening obstetric complications. A birth-preparedness package promotes active preparation and assists in decision-making for healthcare seeking in case of such complications. The aim was to assess factors associated with birth preparedness and complication-readiness as well as the level of male participation in the birth plan among emergency obstetric referrals in rural Uganda.</p> <p>Methods</p> <p>This was a cross-sectional study conducted at Kabale regional hospital maternity ward among 140 women admitted as emergency obstetric referrals in antenatal, labor or the postpartum period. Data was collected on socio-demographics and birth preparedness and what roles spouses were involved in during developing the birth plan. Any woman who attended antenatal care at least 4 times, received health education on pregnancy and childbirth danger signs, saved money for emergencies, made a plan of where to deliver from and made preparations for a birth companion, was deemed as having made a birth plan. Multivariate logistic regression analysis was conducted to analyze factors that were independently associated with having a birth plan.</p> <p>Results</p> <p>The mean age was 26.8 ± 6.6 years, while mean age of the spouse was 32.8 ± 8.3 years. Over 100 (73.8%) women and 75 (55.2%) of their spouses had no formal education or only primary level of education respectively. On multivariable analysis, Primigravidae compared to multigravidae, OR 1.8 95%CI (1.0-3.0), education level of spouse of secondary or higher versus primary level or none, OR 3.8 95%CI (1.2-11.0), formal occupation versus informal occupation of spouse, OR 1.6 95%CI (1.1-2.5), presence of pregnancy complications OR 1.4 95%CI (1.1-2.0) and the anticipated mode of delivery of caesarean section versus vaginal delivery, OR 1.6 95%CI (1.0-2.4) were associated with having a birth plan.</p> <p>Conclusion</p> <p>Individual women, families and communities need to be empowered to contribute positively to making pregnancy safer by making a birth plan.</p

Role of Stem Cells in Human Uterine Leiomyoma Growth

Uterine leiomyoma is the most common benign tumor in reproductive-age women. Each leiomyoma is thought to be a benign monoclonal tumor arising from a single transformed myometrial smooth muscle cell; however, it is not known what leiomyoma cell type is responsible for tumor growth. Thus, we tested the hypothesis that a distinct stem/reservoir cell-enriched population, designated as the leiomyoma-derived side population (LMSP), is responsible for cell proliferation and tumor growth.LMSP comprised approximately 1% of all leiomyoma and 2% of all myometrium-derived cells. All LMSP and leiomyoma-derived main population (LMMP) but none of the side or main population cells isolated from adjacent myometrium carried a mediator complex subunit 12 mutation, a genetic marker of neoplastic transformation. Messenger RNA levels for estrogen receptor-α, progesterone receptor and smooth muscle cell markers were barely detectable and significantly lower in the LMSP compared with the LMMP. LMSP alone did not attach or survive in monolayer culture in the presence or absence of estradiol and progestin, whereas LMMP readily grew under these conditions. LMSP did attach and survive when directly mixed with unsorted myometrial cells in monolayer culture. After resorting and reculturing, LMSP gained full potential of proliferation. Intriguingly, xenografts comprised of LMSP and unsorted myometrial smooth muscle cells grew into relatively large tumors (3.67 ± 1.07 mm(3)), whereas xenografts comprised of LMMP and unsorted myometrial smooth muscle cells produced smaller tumors (0.54 ± 0.20 mm(3), p<0.05, n = 10 paired patient samples). LMSP xenografts displayed significantly higher proliferative activity compared with LMMP xenografts (p<0.05).Our data suggest that LMSP, which have stem/reservoir cell characteristics, are necessary for in vivo growth of leiomyoma xenograft tumors. Lower estrogen and progesterone receptor levels in LMSP suggests an indirect paracrine effect of steroid hormones on stem cells via the mature neighboring cells

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different

Effects of Aging on Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli

Background: Periodontitis is a bacterially induced chronic inflammatory disease. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, termed endotoxin tolerance. Aging has a profound effect on immune response to bacteria challenge. The aim of this study was to explore the effects of aging on endotoxin tolerance induced by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and Escherichia coli (E. coli) LPS in murine peritoneal macrophages. Methodology/Principal Findings: We studied the cytokine production (TNF-aand IL-10) and Toll-like receptor 2, 4 (TLR2, 4) gene and protein expressions in peritoneal macrophages from young (2-month-old) and middle-aged (12-month-old) ICR mice following single or repeated P. gingivalis LPS or E. coli LPS stimulation. Pretreatment of peritoneal macrophages with P. gingivalis LPS or E. coli LPS resulted in a reduction in TNF-a production and an increase in IL-10 production upon secondary stimulation (p,0.05), and the markedly lower levels of TNF-a and higher levels of IL-10 were observed in macrophages from young mice compared with those from middle-aged mice (p,0.05). In addition, LPS restimulations also led to the significantly lower expression levels of TLR2, 4 mRNA and protein in macrophages from young mice (p,0.05). Conclusions/Significance: Repeated LPS stimulations triggered endotoxin tolerance in peritoneal macrophages and the ability to develop tolerance in young mice was more excellent. The impaired ability to develop endotoxin tolerance resulte

Rd9 Is a Naturally Occurring Mouse Model of a Common Form of Retinitis Pigmentosa Caused by Mutations in RPGR-ORF15

Animal models of human disease are an invaluable component of studies aimed at understanding disease pathogenesis and therapeutic possibilities. Mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR) are the most common cause of X-linked retinitis pigmentosa (XLRP) and are estimated to cause 20% of all retinal dystrophy cases. A majority of RPGR mutations are present in ORF15, the purine-rich terminal exon of the predominant splice-variant expressed in retina. Here we describe the genetic and phenotypic characterization of the retinal degeneration 9 (Rd9) strain of mice, a naturally occurring animal model of XLRP. Rd9 mice were found to carry a 32-base-pair duplication within ORF15 that causes a shift in the reading frame that introduces a premature-stop codon. Rpgr ORF15 transcripts, but not protein, were detected in retinas from Rd9/Y male mice that exhibited retinal pathology, including pigment loss and slowly progressing decrease in outer nuclear layer thickness. The levels of rhodopsin and transducin in rod outer segments were also decreased, and M-cone opsin appeared mislocalized within cone photoreceptors. In addition, electroretinogram (ERG) a- and b-wave amplitudes of both Rd9/Y male and Rd9/Rd9 female mice showed moderate gradual reduction that continued to 24 months of age. The presence of multiple retinal features that correlate with findings in individuals with XLRP identifies Rd9 as a valuable model for use in gaining insight into ORF15-associated disease progression and pathogenesis, as well as accelerating the development and testing of therapeutic strategies for this common form of retinal dystrophy

Adenosine A2A receptors: localization and function

Adenosine is an endogenous purine nucleoside present in all mammalian tissues, that originates from the breakdown of ATP. By binding to its four receptor subtypes (A1, A2A, A2B, and A3), adenosine regulates several important physiological functions at both the central and peripheral levels. Therefore, ligands for the different adenosine receptors are attracting increasing attention as new potential drugs to be used in the treatment of several diseases. This chapter is aimed at providing an overview of adenosine metabolism, adenosine receptors localization and their signal transduction pathways. Particular attention will be paid to the biochemistry and pharmacology of A2A receptors, since antagonists of these receptors have emerged as promising new drugs for the treatment of Parkinson's disease. The interactions of A2A receptors with other nonadenosinergic receptors, and the effects of the pharmacological manipulation of A2A receptors on different body organs will be discussed, together with the usefulness of A2A receptor antagonists for the treatment of Parkinson's disease and the potential adverse effects of these drugs