No description available.

No description available.

The blood of man is rich in plasminogen, the inactive precursor of plasmin, a protease (Astrup, 1956a); the most characteristic action of plasmin is the digestion of fibrin, i.e. fibrinolysis. Many tissues, including the prostate (Rasmussen and Albrechtsen, 1960a), contain substances which can activate plasminogen, and thus initiate fibrinolysis, and it has been assumed that both the excessive fibrinolysis seen in the blood of some patients with prostatic disease (Tagnon, Whitmore, Schulman and Kravitz, 1953a), and in prostatic surgery (Lombardo, 1957), is due to the release of this activator into the blood stream (Fearnley, 1965). Human semen contains a substance which can activate the blood fibrinolytic system (von Kaulla and Shettles, 1953). Indeed, when human seminal fluid is ejaculated, it undergoes a process resembling the clotting and fibrinolysis of the blood, by coagulating then liquefying spontaneously. The coagulum is formed when a fibrinogenlike protein secreted by the seminal vesicles is acted upon by a clotting enzyme from the prostate (Mann, 1964). Coagulation is followed within about 20 minutes by liquefactionliquefaction of the clots by an enzyme assumed to come from the prostate (Huggins and Neal, 1942). This enzyme resembles plasmin in that it is a protease acting on a fibrin-like substrate, and that it is derived from an inactive precursor.

No description available.

Sexual transmission of the Human Immunodeficiency Virus Type 1 (HIV-1) accounts for the majority of newly acquired infections. Vaccination efforts have induced only modest protection in HIV clinical trials. HIV-1 induces a robust local immune response in genital mucosa of exposed individuals. Understanding the function of naturally occurring antibodies against HIV-1 in genital mucosa, the primary site of transmission, might be instrumental to improving vaccines and antibody-based microbicides. This study focused on HIV-specific antibody responses in the male genital tract (MGT), which is underexplored. We characterized antibody subclasses and specificities in genital tract secretions (seminal plasma, urethral secretions) and blood from a cohort of HIV-1-infected men to determine the origin and distinct nature of antibodies in the MGT. We detected similar HIV-1 IgG titers and specificities in all three body fluids, indicating that MGT IgG likely originates from blood. In contrast, gp41-specific IgA was restricted to genital secretions suggesting a local niche of IgA antibody production. Genital secretions from a subset of individuals neutralized cell-free HIV-1 and blocked cell-to-cell HIV-1 transmission. Statistically, these functions correlated positively with gp41 IgA titers. HIV-specific IgA monoclonal antibodies were also effective in these assays. To explore cell-dependent activities of HIV-specific antibodies in genital mucosa we surveyed Fc receptor expression in mucosal epithelial tissue. The IgG-engaging neonatal Fc receptor (FcRn), the IgA receptor FcαRI and the high-affinity intracellular Fc receptor TRIM21 were detected by immunohistochemistry and western blots. In stratified squamous epithelia (foreskin, vagina) FcRn+ epithelial cells were detected primarily in the basal layer, FcαRI+ epithelial cells in suprabasal layers and TRIM21 throughout. Deposits of immunoglobulins in the stratified squamous epithelium colocalized with FcRn, FcαRI and TRIM21. Our findings indicate that the MGT is capable of expressing a local anti-HIV IgA response to achieve antiviral defense through antibody neutralization and cell-dependent functions involving classical immune effector cells and epithelial cells.

Thirty five million people are currently living with HIV-1 today with women accounting for half of infected individuals globally. Sexual transmission is the main route of HIV transmission with approximately 40% of HIV infections occurring when the mucosal lining of the female genital tract (FGT) is exposed to HIV in semen from an infected male partner. Seminal plasma (SP), the fluid portion of semen, is a complex fluid which plays an immunomodulatory role in the FGT for successful conception, largely due to its high concentrations of TGF-β1. Several factors in SP from HIV-uninfected men have been shown to either inhibit or enhance HIV infection in target cells, however it is not clear how SP from HIV infected men would modulate genital epithelial cells (GECs), the first cells that encounter HIV in the FGT. The overall goals of this thesis were to compare inflammatory and regulatory cytokine concentrations in SP from HIV-uninfected and infected men, and subsequently compare GEC cytokine responses following exposure to SP from HIV-uninfected and HIV-infected men. I also investigated how SP and TGF-β regulated cytokine production and barrier function in GECs in the presence of HIV. The results summarized in this thesis demonstrated that HIV infection leads to different cytokine profiles in SP, based on stage of HIV-1 infection. HIV-infected men in acute stage contained higher levels of proinflammatory cytokines in their SP compared to HIV-uninfected and chronically infected men (CI men) which subsequently lead to higher levels of proinflammatory cytokines from GECs compared to CI men. In the follow up to this study we found that active TGF-β, which was found in higher concentrations in SP from CI men and led to decreased inflammatory response from GECs, was compartmentalized between blood plasma and seminal plasma. Higher levels of active TGF-β in SP correlated with decreased semen viral load and the immune activation marker sCD14 leading us to believe that ART-naive CI men in our cohort were naturally controlling their immune activation status, as active TGF-β levels were lower in ART-treated men. Short-term exposure of GECs to SP from CI men or TGF-β at comparable concentrations to SP protected the GEC barrier against HIV by decreasing inflammatory cytokines and preventing tight junction breakage. However, long-term exposure to TGF-β in the presence of HIV further increased inflammation in GECs suggesting a biphasic role for TGF-β in the FGT. This body of work summarized in this thesis demonstrates for the first time how semen from HIV-infected men modulates FGT epithelial cell cytokine responses and barrier function, an important consideration in the design of local therapeutic strategies to protect the FGT against HIV infection. / Thesis / Doctor of Philosophy (Medical Science)

Sarcomas of the female genital tract are rare tumors and account for less than 5% of gynecologic malignancies. Traditionally, gynecologic sarcomas have been divided into different tumor types according to their histopathological features. The most common are leiomyosarcoma (LMS), malignant mixed Müllerian tumors (MMMT), endometrial stromal sarcoma (ESS) and (Müllerian) adenosarcoma. The different tumor types are highly aggressive with early lymphatic and/or hematogenous spread. Treatment is difficult and it is believed that sarcomas have a low radio-and chemosensitivity, and the mainstay in treatment is surgical removal of the tumor. The most important prognostic feature has been tumor stage. Nevertheless, there are some early-stage tumors that run a biological course different from that expected and additional prognostic factors indicating high-risk tumors are desirable. The study cohort consists of 49 uterine LMS, 44 uterine MMMTs, 17 uterine ESS, 11 uterine adenosarcomas and 26 ovarian MMMTs. The tumors were analyzed in a retrospective manner for DNA ploidy, S-phase fraction (SPF), p53 and mdm-2 expression, as well as traditional clinical and pathological prognostic factors, such as tumor stage. grade, atypia and mitotic index. Of the 49 LMS, 36 (86%) were non-diploid and 13 (27%) were p53-positive. Among the 44 uterine MMMTs, 30 (68%) were non-diploid and 27 (61%) had an SPF>10%. Twenty-seven (61%) overexpressed p53 and 11 (25%) were mdm-2 positive. Furthermore, 40 (91%) of the uterine MMMTs had a high mitotic count and 42 (95%) had high grade cytologic atypia. All low-grade ESS were DNA diploid and had a low SPF. Among the four high-grade ESS, three (75%) were DNA aneuploid and three (75%) were p53-positive. Among 1 1 adenosarcomas, eight (73%) were non-diploid. All ovarian MMMTs were non-diploid and all but two had an SPF>10%. 19 (73%) ovarian MMMTs were p53positive. The 5-year survival rate was 33% for LMS, 38% for uterine MMMT, 57% for ESS, 69% for adenosarcoma and 30% for ovarian MMMT. Thirty-five (71%) patients with LMS died of disease and two of intercurrent disease. Stage was found to be the most important factor for survival (p=0.007); in addition DNA ploidy (p=0.045) and SPF (p=0.041) had prognostic significance. Twenty-seven (61%) patients with uterine MMMT died of disease and six (14%) died of intercurrent disease. Stage was the only prognostic factor for survival. Nine (53%) patients with ESS died of disease. There was a significant correlation of survival to tumor grade (p=0.007), DNA ploidy (p=0.026), SPF (p=0.048) and stage (p=0.026). Of the 11 patients with adenosarcoma, four (36%) patients died of disease and three (27%) patients died of intercurrent disease. There were no variables that correlated with survival. Eighteen (69%) patients with ovarian MMMT died of disease and two (8%) patients died of intercurrent disease. In a multivariate analysis, only stage reached independent prognostic significance for survival (p=0.023). In summary, stage represents the most important prognostic factor for survival for uterine and ovarian sarcomas. DNA flow cytometry is useful in gaining additional prognostic information for LMS and ESS. P53-and mdm-2 overexpression had no prognostic value for survival rate. Most of the MMMT overexpressed p53 and were non-diploid. Treatment of sarcomatous neoplasms is difficult and the mainstay remains surgical removal of the tumor. For patients with early stage sarcoma there was a high recurrence rate, which suggests that a large proportion of patients may have systemic micrometastasic disease at the time of diagnosis. Recurrent and metastatic uterine sarcoma remains an incurable disease, and treatment must be considered palliative. / On the day of the public defence the status of the articles III and IV was: Accepted for publication. ; Bild/Image 1=p53/mdm-2 interaction ; Bild/Image 2=Leiomysarcoma stage I ; Bild/Image 3=Survival in uterine sarcoma.

1.The prevalence of sow reproductive organ disease was ascertained in the Lithuania’s Republic’s large hog complexes; 2.The dominating microflora in sow reproductive organs and its influence in post-weaning fertilisation were established; 3.The influence of prophylactic use of recommended feed supplements Spectinomix 110 and Lincosint 100 on reproductive organ microflora and piglet to weaning health was evaluated; 4.The prophylactic and treatment efficacy of veterinary preparations 2.5% sol. Cobactan®, Metricure®, Clamoxyl ® Metritis was established in sows with post-partum uterine inflammations.

Thesis (MScMedSc)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The basic semen analysis plays a pivotal role in the diagnosis of male infertility and makes a significant contribution to the diagnostic process in andrology, gynecology and clinical urology. In 1902, the man considered to be ―the founding father of modern andrology‖ Edward Martin, proposed that an analysis of a semen sample should be incorporated into all infertility assessments. Following this suggestion in 1956, the scientist John MacLeod advanced the basic semen analysis from beyond a mere observation and introduced the importance of certain semen parameters such as morphology, motility and viscosity. The present day examination includes the analysis of certain established semen parameters, which can provide key information about the quality of a patient‘s semen and the functional competence of the spermatozoa. A semen analysis is also a valuable diagnostic tool in assessing possible disorders of the male genital tract and the secretory pattern of the male accessory sex glands. This information can help to determine the reproductive capacity of the male and can be used in conjunction with the partner to indicate the impact of male genital pathophysiology in the assessment of a couple‘s prospect for fertility. Patients attending the andrology laboratory at Tygerberg Academic Hospital for a semen analysis are referred based on primary, secondary or idiopathic infertility. Amongst these patients, an increase in semen viscosity has been observed over a period of time and created the need to assess the possible causes behind this trend. Despite viscosity being included in a routine spermiogram, it raises a considerable amount of concern as it is assessed semi-quantitatively. In the first part of this study, the possible correlation between seminal hyperviscosity and leukocytospermia was assessed. To achieve the most comprehensive assessment of viscosity, a new approach was used, which is a highly quantitative method to record viscosity in the international unit, centipoise (cP). The analysis of semen samples for possible leukocytospermia was approached by three methods the first of which was cytological. During this method granulocyte grading was performed on stained semen smears during the normal determination of morphology. The same approach was taken for the second method, whereby white blood cell concentrations were quantified with a leukocyte peroxidase test in the total sample group (n=200). Viscosity was compared between the samples classified as leukocytospermic positive or negative, according to the set reference values of the World Health Organisation (WHO). Correlation analysis between the two variables was also performed. In the biochemical approach of detecting leukocytospermia, an enzyme-linked immunoabsorbant assay (ELISA) was used to quantify the concentration of the extracellular polymorphonuclear (PMN) enzyme released from leukocytes. This test was performed on 124 randomly selected samples. All samples were fractionated before storage in liquid nitrogen, to allow for multiple assessments to be performed on each sample. The PMN elastase concentration was assessed against viscosity to investigate a possible correlation and relationship with the presence of leukocytospermia. All three methods of detecting possible infection showed a significantly positive relationship with increased viscosity in semen samples. The second approach in the study was to assess increased viscosity and leukocytospermia against parameters included in the spermiogram. An evaluation of hyperviscosity and its correlations to the various other semen parameters can allow for a detailed study into the effects that this anomaly may elicit. With the assessment of each of the sperm parameters against the leukocyte count and viscosity (cP), volume, concentration and morphology showed significance. To further the study, the third angle was to investigate a possible correlation between viscosity and the functional status of the male accessory sex glands. The biochemical approach of assessing the secretory patterns of the prostate and seminal vesicles against markers of infection can possibly further the understanding behind hyperviscous semen and leukocytospermia. Citric acid and fructose, secretory products of the prostate and seminal vesicles respectively, showed no significance when assessed against the leukocyte count and viscosity. However, this project was a pilot study and this approach offers an exciting avenue for further research. These research findings may provide a more comprehensive assessment of a man‘s fertility status. Seen in the context of patients attending the andrology laboratory of Tygerberg Academic Hospital, this is greatly needed as the majority of these patients cannot afford advanced assisted reproductive therapies. The introduction of a more accurate method of quantifying viscosity may possibly help to identify, diagnose and treat patients suffering from leukocytospermia in order to ultimately enhance their fertility potential. / AFRIKAANSE OPSOMMING: Die basiese semenanalise speel 'n belangrike rol in die diagnose van manlike infertiliteit en maak dus 'n betekenisvolle bydrae tot die diagnostiese proses in andrologie, ginekologie en kliniese urologie. In 1902 het Edward Martin, wat deur sommige navorsers as die vader van moderne andrologie beskou word, voorgestel dat 'n semenanalise deel moet vorm van alle infertiliteitsondersoeke. In 1956 het die wetenskaplike John MacLeod aanvoorwerk gedoen om die grondslag van 'n basiese semenanalise daar te stel, wat beteken het dat, in plaas van net 'n observasie studie te doen, 'n semenmonster kwantitatief analiseer moes word en dat parameters soos spermmorfologie, motiliteit en viskositeit as deel van die volledige analise gedoen moet word. Die hedendaagse analise sluit, behalwe die basiese semenparameters, ook inligting in oor die funksionele aspekte van spermatozoa. Die semenanalise is dus ook ‗n belangrike diagnostiese hulpmiddel om inligting rakende moontlike abnormaliteite in die manlike genitale traktus en die sekretoriese funksies van die manlike bykomstige geslagskliere te verskaf. Hierdie inligting kan help om 'n moontlike diagnose van die man se fertiliteitspotensiaal te maak. Terselftertyd kan dit ook tesame met die metgesel se reproduktiewe inligting meer lig werp op die impak van die man se genitale patofisiologie op die paartjie se fertilitetspotensiaal. Pasiënte wat die andrologielaboratorium van die Tygerberg Akademiese Hospitaal besoek word verwys op grond van primêre, sekondêre of idopatiese infertiliteit. Gedurende die laaste aantal jare is daar ‗n toename in voorkoms van verhoogde semenviskositeit onder hierdie groep pasiënte waargeneem. Dit het die behoefte laat ontstaan om die moontlike redes hiervoor te ondersoek. Ten spyte van die feit dat viskositeit deel vorm van die roetine semenanalise is dit tog kommerwekkend aangesien dit op 'n semi-kwantitatiewe manier bepaal word. In die eerste deel van hierdie studie is 'n moontlik korrelasie tussen seminale hiperviskositeit en leukositospermie ondersoek. Om die beste moontlike verwantskap te kon bepaal is 'n nuwe en hoogs kwantitatiewe metode gebruik om viskositeit in numeriese waardes volgens internasionale standaarde in centipoise (cP) te meet. Daar is van drie metodes gebruik gemaak om die teenwoordigheid van leukositospermie in 'n semenmonster te ondersoek. Die eerste metode was die sitologiese metode waar die teenwoordigheid van granulosiet op die gekleurde semensmeer tydens die standaard morfologie beoordeling bepaal word. Die tweede was deur middel van 'n leukosietperoksidase toets waarmee daar 'n kwantitatiewe telling gedoen kan word, soos teenwoordig in 'n voorbereide semenmonster. Hierdie twee bepalings is op die totale studiepopulasie van 200 pasiënte gedoen. Die viskositeit van monsters met of sonder die teenwoordigheid van leukositospermie, soos bepaal met die voorafgaande metodes en gebaseer op die WGO riglyne, is met mekaar vergelyk. Korrelasies is ook tussen hierdie twee veranderlikes en verskeie semenparameters van hierdie twee groepe gedoen. Die derde metode was 'n biochemiese ontleding met behulp van 'n ensiemgekoppeldeimmuunsorberende essai (ELISA) vir die bepaling van die ekstrasellulêre konsentrasie van polimorfonukleêre (PMN) elastase ensiem in die seminale plasma. Hierdie toets is op 124 lukraak gekose semenmonsters uitgevoer. Alle monsters is gefraksioneer voor berging in vloeibare stikstof om meervoudige analises van elke monster moontlik te maak. Die PMN elastase konsentrasies is vergelyk met die viskositeit van die semenmonsters vir 'n moontlike korrelasie en verwantskap met die teenwoordigheid van leukositospermie. Die resultate van al drie hierdie metodes, vir die moontlike bepaling van infeksie, het 'n betekenisvolle positiewe verwantskap met die toename in graad van viskositeit in semenmonsters aangetoon. Die tweede benadering van hierdie studie was om die viskositeitsgradering en die kwantitatiewe leukositopermie waardes te vergelyk met die semenparameters wat bepaal is tydens die semenanalise. Die doel van hierdie benadering was om enige verwantskap of effek van viskositeit asook die teenwoordigheid van witbloedselle op die semenparameters te ondersoek. Daar is betekenisvolle verwantskappe gevind tussen die viskositeitstatus van 'n semenmonster, die teenwoordigheid van witbloedselle en die semenparameters, soos motiliteit, morfologie en spermatosoa konsentrasie. Die derde benadering was om 'n ondersoek te doen na die moontlike verwantskap tussen viskositeit en die sekretoriese funksies van die manlike bykomstige geslagskliere, te wete die prostaat en seminale vesikula. Die biochemiese ondersoek na die sekresies van hierdie twee organe, naamlik fruktose en sitroensuur, is gedoen om te bepaal of die teenwoordigheid van infeksies van die manlike traktus, en waargeneem as leukositospermia, ook in verband gebring kan word met die viskositeitstatus van 'n semenmonster. Daar is geen verband gevind tussen die sekresies van hierdie twee kliere en die viskositeit van die semenmonsters nie. Aangesien hierdie deel van die studie net as 'n loodsprojek beskou is, is die biochemiese bepalings slegs op 'n beperkte aantal semenmonsters uitgevoer en kan hierdie tipe ondersoek as 'n moontlike verdere studie onderneem word. Hierdie navorsingsresultate kan lei tot ‗n meer omvattende assessering van mans se fertiliteitstatus. Dit is uiters noodsaaklik in die konteks van omstandighede van die pasiënte wat die andrologielaboratorium van die Tygerberg Akademiese Hospitaal besoek aangesien die meerderheid nie gevorderde in vitro behandeling kan bekostig nie. Die akkurate bepaling van 'n semenmonster se viskositeit kan dus moontlik waarde toevoeg tot die identifisering, diagnose en behandeling van pasiënte met leukositospermie om sodoende hulle fertiliteitspotensiaal te verbeter.

The immune-reactive sperm are kept separate from the body by epithelial barriers such as the blood-testis barrier (BTB). While these barriers are beneficial for the protection of sperm from toxicants, they can make treating these areas difficult due to preventing the entry of pharmacological agents. This is especially an issue in the treatment of HIV and Ebola infection based on the ample evidence that these viruses are able to survive and spread from within the male genital tract (MGT), but only a few antiviral drugs are known to access the MGT. Transporters that line the epithelial barriers of the MGT, especially the BTB, are important for determining whether or not a drug is able to penetrate into the MGT through transepithelial transport. Several nucleoside analogs (NSA), which are used to treat HIV infection and leukemias, are known to be able to accumulate in seminal plasma, which makes them a useful tool for understanding transepithelial transport for the BTB. The purpose of these studies is to characterize the transport profile for the MGT, in particular the BTB, to gain a better understanding of how xenobiotics, especially ones based on nucleosides, can access the MGT. The chief finding of this work is the discovery of a transepithelial transport pathway expressed by Sertoli cells that allows for the entry of nucleosides (necessary for germ cell development) and NSA into the MGT. This pathway depends on equilibrative nucleoside transporter (ENT) 1 uptake and ENT2 efflux and occurs in both rats and humans. These studies provide the foundation for being able to predict the penetration of novel drugs into the MGT.