Regional Differences in the Tunica Media of the Uterine Artery of Domestic Pig (Sus Scrofa Domesticus): Basis for Uterine Blood Flow Regulation

This study aimed at describing the structure of tunica media of the uterine artery of domestic pig, since this structure influences the pattern of blood flow and reproductive performance. Specimens were obtained from main trunk, broad ligament segment and the terminal portion of twelve healthy adult domestic pigs (Sus scrofa domesticus) age range 6 – 18 months. They were fixed in 10% formaldehyde solution, and routinely processed for paraffin embedding and sectioning. Seven micron thick sections were stained with Hematoxylin & Eosin, Mason’s Trichrome and Weigert resorcin fuchsin counterstained with Van Gieson stains. Tunica media comprising predominantly smooth muscle occupied approximately fifty percent (50%) of the volume of the entire wall with vasa vasora present deep into its inner zone. It showed zonal and regional variation in that in the main trunk and broad ligament segments was divided into inner two thirds having   predominantly circular smooth muscle orientation while outer third was  preponderantly fibroelastic with longitudinally disposed smooth muscles. The terminal segment had only circular layer. Density of vasa vasora  declined distally. The predominantly muscular tunica media of the uterine artery in pigs shows zonal and regional suggesting segmental   differentiation of function. The main trunk of this artery, due to its  additional longitudinal layer of smooth muscle may be involved in  regulation of blood flow to the uterus depending on the functional  demands of the uterus

PAI-1 secretion of endometrial and endometriotic cells is Smad2/3- and ERK1/2-dependent and influences cell adhesion

In the endometrium transforming growth factor-betas (TGF-ßs) are involved mainly in menstruation and endometriosis. After binding of the ligands to the high-affinity receptors, TGF-ß receptors (TBR1 and TBR2), TGF-ßs activate Smad signaling to modulate gene expression and cellular functions. However, recently also Smad-independent pathways have been studied in more details. To evaluate both pathways, we have analyzed TGF-ß signaling in human endometrial and endometriotic cells. Although endometrial and endometriotic cells secrete TGF-ß1, secretion by stromal cells was higher compared to epithelial cells. In contrast, secretion of TGF-ß2 was higher in endometriotic stromal and endometriotic epithelial cells compared to normal endometrial cells. Treatment of endometrial and endometriotic stromal and epithelial cells with TGF-ß1 or TGF-ß2 increased Smad-dependent secretion of plasminogen activator inhibitor-1 (PAI-1) dramatically in all three cell lines. Of note, endometriotic cells secreted clearly higher levels of PAI-1 compared to endometrial cells. Whereas a TBR1 kinase inhibitor completely blocked the TGF-ß1 or TGF-ß2-induced PAI-1 secretion, an ERK1/2 inhibitor only partially reduced PAI-1 secretion. This inhibition was not dependent on epidermal growth factor receptor (EGFR) activation by phosphorylation but on kinase activity of the TBR1. Finally, treatment of endometrial and endometriotic cell lines with recombinant PAI-1 showed reduced cell adhesion, especially of the endometrial cells. In summary, our results demonstrate that both Smad-dependent and TBR1-dependent ERK1/2 pathways are necessary for TGF-ß-dependent high level secretion of PAI-1, which might increase cellular deadhesion

Endometriosis among African women

Endometriosis has long been wrongly perceived to be rare among women of African descent. The misconception about the prevalence of endometriosis among African women has significantly contributed to long diagnostic delays, limited access to diagnosis and care, and a scarcity of research on the condition among African women. In this commentary, we highlight the prevalence of endometriosis among African women, the state of endometriosis care in Africa, and the gaps in knowledge that need to be addressed. Based on the available data, the prevalence of endometriosis in Africa is likely higher than previously thought, with varying subtypes. There is a long diagnostic delay of endometriosis among African women. Additionally, endometriosis care in Africa from the general population and health practitioners is poor; this can be attributed to the high diagnostic cost, scarcity of trained specialists, as well as patients’ inability to express their symptoms due to societal taboos surrounding menstrual health. Public sensitization on endometriosis may help improve endometriosis diagnosis and care in Africa. LAY SUMMARY: Endometriosis is a condition in which tissue like the uterine lining is found outside the uterus, causing women to experience pain especially before, during, or after menstruation. Although endometriosis affects an estimated 176 million women worldwide, it has been wrongly reported that endometriosis is a rare condition among African women, mainly due to lack of awareness among healthcare providers and historical bias. In the current commentary, we discuss the prevalence of endometriosis, the diagnostic delays, and the care of endometriosis among black African women living in the African continent. Much of the literature has demonstrated (falsely) that endometriosis is rare in Black women compared to White ethnicity. African women experience a long diagnostic delay and do not receive appropriate care. Public awareness of endometriosis may help improve diagnosis delay and endometriosis care in Africa

Transforming growth factor-β induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis

CONTEXT: TGF-β is believed to play a major role in the etiology of peritoneal endometriosis. In tumors, TGF-β induces the metabolic conversion of glucose to lactate via glycolysis, a process referred to as the “Warburg effect.” Lactate increases cell invasion, angiogenesis, and immune suppression, all crucial steps in the development of endometriosis. OBJECTIVE: The aim of this study was to determine whether TGF-β induces a “Warburg-like” effect in peritoneal endometriosis. DESIGN: The study was informed by human tissue analysis and cel culture. SETTING: The study was conducted at the university research institute. PATIENTS OR OTHER PARTICIPANTS: We studied women undergoing surgical investigation for endometriosis. INTERVENTIONS: Concentrations of lactate and TGF-β1 in peritoneal fluid (n = 16) were measured by commercial assay. Expression of genes implicated in glycolysis was measured in endometrial and peritoneal biopsies (n = 31) by quantitative RT-PCR and immunohistochemistry. The effect of TGF-β1 on primary human peritoneal mesothelial cells (n = 6) and immortalized mesothelial (MeT-5A) cells (n = 3) was assessed by quantitative RT-PCR, Western blot, and commercial assays. MAIN OUTCOME MEASURES: Lactate, TGF-β1, and markers of glycolysis were measured. RESULTS: Concentrations of lactate in peritoneal fluid paralleled those of TGF-β1, being significantly higher in women with endometriosis compared to women without (P < .05). Endometriosis lesions expressed higher levels of glycolysis-associated genes HIF1A, PDK1, and LDHA than eutopic endometrium, and adjacent peritoneum had higher levels of HIF1A and SLC2A1 than peritoneum from women without disease (P < .05 to P < .001). Exposure of mesothelial cells to TGF-β1 increased production of lactate (P < .05), increased HIF1A mRNA (P < .05), and protein, and increased concentrations of mRNAs encoded by glycolysis-associated genes (LDHA, PDK1, SLC2A1; P < .05). CONCLUSIONS: A change in the metabolic phenotype of endometriosis lesions and peritoneal mesothelium in women with endometriosis may favor development of endometriosis

The Peritoneum Is Both a Source and Target of TGF-β in Women with Endometriosis

Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05) and peritoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (P<0.05). The TGF-β-stimulated Smad 2/3 signalling pathway was active in the peritoneum and there were significant increases (P<0.05) in expression of genes associated with tumorigenesis (MAPK8, CDC6), epithelial-mesenchymal transition (NOTCH1), angiogenesis (ID1, ID3) and neurogenesis (CREB1) in the peritoneum of women with endometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation

CELLULAR AND MOLECULAR INTERACTIONS IN HIV INFECTIONS: A REVIEW

Objective: To review the cellular and molecular interactions between HIV and the hostimmune system that lead to full-blown AIDS.Data Sources: Published reports on HIV/host interaction during a fifteen year periodbeginning from 1987.Study selection: Only those studies involving humans and non-human primates wereselected. The studies included original articles and state-of-the-art reviews covering in vivoand in vitro findings.Data extraction and synthesis: This article presents a critical review of the cellular andmolecular mechanisms of HIV infection and their relationship to the onset of AIDS.Conclusion: HIV has elaborated diverse and somewhat complicated mechanisms for thesubversion and evasion of the host immune defence strategies. These include escape throughmutation, prolonged latency of the infection, masking of the viral envelope proteins, downregulationof MHC-I and up-regulation of the Fas-ligand on infected cell surfaces. Thisreview enhances our understanding of HIV/AIDS disease and presents a basis on whichmanagement strategies could be developed

Correlation between morphometry of the uterine artery and estradiol levels in non pregnant domestic pigs (sus scrofa domesticus)

Background: Structure and morphometry of the uterine artery are important in influencing the pattern of blood flow to the uterus and may be affected by the levels of estradiol. Consequently these may have an effect on reproductive performance.Objective: This study aimed at describing the relation between morphometry of uterine artery from domestic pigs and 17 Beta estradiol.Design: Descriptive cross sectional study.Methods: Blood samples and specimens of uterine artery were obtained from twelve healthy female domestic pigs (Sus scrofa domesticus). They were fixed in 10% formaldehyde solution, and routinely processed for paraffin embedding. Seven micron thick sections were stained with Mason’s Trichrome. Morphometric parameters were measured using Scion image analyzer and estradiol levels assayed by enzyme linked immunoassay technique.Results: The thickness of uterine artery and its luminal diameter increased with advancing age. The level of 17 Beta - Estradiol also steadily rose with age and plateaued by 17th week of domestic pigs’ life. Estradiol had a positive effect on growth and development of the uterine artery wall components. Notably, it hada significant growth effect on the tunica media and the overall thickness of the uterine artery and had an apparent luminal narrowing effect.Conclusion: The present study reveals that estrogen may be considered as an important hormone in preservation of uterine arterial wall integrity. It is associated with changes in the uterine artery dimensions important in preparation for increased volume of blood flowing to the uterus prior to the reproductive act.Keywords: Uterine artery, Non pregnant, Pig, Morphometry, Estradio

Cellular and molecular interaction in HIV infection: A review

Objective: To review the cellular and molecular interactions between HIV and the host immune system that lead to full-blown AIDS. Data Sources: Published reports on HIV/host interaction during a fifteen year period beginning from 1987. Study selection: Only those studies involving humans and non-human primates were selected. The studies included original articles and state-of-the-art reviews covering in vivo and in vitro findings. Data extraction and synthesis: This article presents a critical review of the cellular and molecular mechanisms of HIV infection and their relationship to the onset of AIDS. Conclusion: HIV has elaborated diverse and somewhat complicated mechanisms for the subversion and evasion of the host immune defence strategies. These include escape through mutation, prolonged latency of the infection, masking of the viral envelope proteins, downregulation of MHC-I and up-regulation of the Fas-ligand on infected cell surfaces. This review enhances our understanding of HIV/AIDS disease and presents a basis on which management strategies could be developed. (East African Medical Journal: 2002 79(5): 249-253

Possible immunological basis for recurrent spontaneous abortion: a review

(East African Medical Journal 2001: 78 (11): 586-589