The African National Congress's factionalism and targeted killings as risks to human security in KwaZulu-Natal province.

A prevalence of political violence and political assassinations characterised post-1994 South Africa. These politically motivated killings appeared to be dominant in the controversial KwaZulu-Natal (KZN) province. Political killings in South Africa started as a form of inter-party warfare, especially during the transition to democracy, when the two rivals, the African National Congress (ANC) and the Inkatha Freedom Party (IFP), fought each other for some areas of Gauteng and KwaZulu-Natal provinces. However, following the dominance of the ANC in the KZN Province, members of the ruling party fought each other for positions in government and political party structures. Considering this, the article analyses the crisis of factionalism by examining the ANC's intra-party tensions and targeted killings, and how this poses a risk to human security in KZN. Methodologically, the article employs a qualitative literature assessment and content analysis is used to delve into the impact of intra-party tensions and targeted killings on human security in the KZN province. Contribution: In quest for curbing the crisis of factionalism in the ruling ANC, the article recommends that the ANC needs to re-visit its leadership selection as these killings have seemingly happened during leadership selection, which leads to ruthless competition of positions in government and party structures. Members of the ruling party need to identify themselves as one, as opposed to belonging to different factional groups within the party. Failure by the ruling party to address divisions within the organisation shall result in more fatal killings resulting from competition for positions and resources.

Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Postmenopausal Women.

BACKGROUND: Sex hormone (SH) imbalances have been linked to a higher risk of heart failure in both sexes. However, mechanisms that underlie this relationship remain unclear. We examined the association of baseline SH with interstitial and replacement myocardial fibrosis in the MESA (Multi-Ethnic Study of Atherosclerosis) using cardiac magnetic resonance (CMR) T1 mapping and late gadolinium enhancement (LGE). OBJECTIVES: The purpose of this study was to assess the link between baseline sex hormone levels and myocardial fibrosis in the MESA cohort using CMR. METHODS: A total of 2,324 participants (men and postmenopausal women [PMW]) were included in the MESA with SH measured at baseline and had underwent CMR 10 years later. All analyses were stratified by sex and age. Regression models were constructed to assess the associations of baseline SH with extracellular volume (ECV)% and native T1 time and with LGE. Higher native T1 time and ECV% are interpreted as evidence of increasing interstitial myocardial fibrosis (IMF). Given the limited number of myocardial scars present in PMW, analysis of LGE was limited to men. RESULTS: Among older men (age ≥65 years), a 1-SD increment higher free testosterone was significantly associated with 2.45% lower ECV% and 21.5% lower native T1 time, while a 1-SD increment higher bioavailable testosterone was associated with 12.5% lower native T1 time. A 1-SD increment greater sex hormone-binding globulin level was associated with 1% higher ECV%. Among PMW of 55 to 64 years, a 1-SD increment higher total testosterone was associated with 9.5% lower native T1 time. Higher levels of estradiol in older men were independently associated with higher odds of having a myocardial scar (OR: 4.10; 95% CI: 1.35-12.40; P = 0.01). CONCLUSIONS: Among older men, SH imbalances at initial evaluation were independently associated with CMR defined IMF and replacement fibrosis, respectively; while increasing total testosterone in middle-aged PMW was associated with lesser marker of IMF. (JACC Adv 2023;2:100320) Published by Elsevier on behalf of the American College of Cardiology Foundation.

Testicular damage by microcirculatory disruption and colonization of an immune-privileged site during Borrelia crocidurae infection.

The agent of African relapsing fever, Borrelia crocidurae, causes reversible multiple organ damage. We hypothesize that this damage is caused when the spirochete forms aggregate with erythrocytes in vivo, creating rosettes that plug the microcirculatory system. To test this hypothesis, we compared testicular microcirculation over an extended time period in two groups of rats: one experimentally inoculated with B. crocidurae, the other with the nonerythrocyte rosette-forming Borrelia hermsii. In the B. crocidurae group, erythrocyte rosettes formed during spiro-chetemia blocked precapillary blood vessels and reduced the normal pattern of microcirculatory blood flow. After spirochetemia, erythrocyte rosettes disappeared and flow was normalized. Decreased blood flow and focal vascular damage with increased permeability and interstitial bleeding adjacent to the erythrocyte microemboli induced cell death in seminiferous tubules. Interestingly, we found that B. crocidurae could penetrate the tubules and remain in the testis long after the end of spirochetemia, suggesting that the testis can serve as a reservoir for this bacteria in subsequent relapses. The group infected with B. hermsii displayed normal testicular blood flow and vasomotion at all selected time points, and suffered no testicular damage. These results confirmed our hypothesis that the erythrocyte rosettes produce vascular obstruction and are the main cause of histopathology seen in model animal and human infections.

AphidBase: a centralized bioinformatic resource for annotation of the pea aphid genome.

AphidBase is a centralized bioinformatic resource that was developed to facilitate community annotation of the pea aphid genome by the International Aphid Genomics Consortium (IAGC). The AphidBase Information System designed to organize and distribute genomic data and annotations for a large international community was constructed using open source software tools from the Generic Model Organism Database (GMOD). The system includes Apollo and GBrowse utilities as well as a wiki, blast search capabilities and a full text search engine. AphidBase strongly supported community cooperation and coordination in the curation of gene models during community annotation of the pea aphid genome. AphidBase can be accessed at http://www.aphidbase.com.

Global analysis of endothelial cell line proliferation patterns based on nutrient-depletion models: implications for a standardization of cell proliferation assays.

It is known that cell populations growing in different environmental conditions may exhibit different proliferation patterns. However, it is not clear if, despite the diversity of the so-observed patterns, inherent cellular growth characteristics of the population can nevertheless be determined. This study quantifies the proliferative behaviour of the permanent endothelial human cell line, Eahy926, and establishes to which extent the estimation of the cell proliferation rate depends on variations of the experimental protocols. Cell proliferation curves were obtained for cells cultured over 16 days and the influences of cell seeding densities, foetal bovine serum content and frequency of culture medium changes were investigated. Quantitative dynamic modelling was conducted to evaluate the kinetic characteristics of this cell population. We proposed successive models and retained a nutrient-depletion toxicity dependant model, which takes into account the progressive depletion of nutrients, as well as the increase of toxicity in the cell culture medium. This model is shown to provide a very good and robust prediction of the experimental proliferation curves, whatever are the considered frequency of culture medium changes and serum concentrations. Thus, the model enables an intrinsic quantification of the parameters driving in vitro EAhy926 proliferation, including proliferation, nutrient consumption and toxicity increase rates, rather independently of the experiments design. We therefore propose that such models could provide a basis for a standardized quantification of intrinsic cell proliferation kinetics.

KID, a Kinase Inhibitor Database project.

The Kinase Inhibitor Database is a small specialized database dedicated to the gathering of information on protein kinase inhibitors. The database is accessible through the World Wide Web system and gives access to structural and bibliographic information on protein kinase inhibitors. The data in the database will be collected and submitted by researchers working in the kinase inhibitor field. The submitted data will be checked by the curator of the database before entry.

Localization and effects of calcitonin gene-related peptide in the testicular vasculature of the rat.

UNLABELLED: Using laser Doppler flowmetry, the effects of unilateral intratesticular injection of calcitonin gene-related peptide (CGRP) and CGRP8-37, a CGRP-receptor antagonist, on right- and left-testicular blood flow and mean arterial pressure were studied on anesthetized adult rats. Calcitonin gene-related peptide in doses of 5 and 50 ng increased blood flow 37 +/- 11% (mean +/- SEM, P < 0.05) and 30 +/- 5% at 5 mm, but not 15 mm, away from the injection site, respectively. They did not influence mean arterial pressure nor blood flow in the contralateral testis. Five-hundred nanogram doses increased testicular blood flow in the injected testis at a point 15 mm away from the injection site (22 +/- 3%, P < 0.05) and caused a slight decrease in mean arterial pressure (-12 +/- 3%, P < 0.05). The highest dose, 5 micrograms, caused a large (-39 +/- 3%, P < 0.05) fall in mean arterial pressure within 1 minute after injection, and testicular blood flow was reduced in both the injected (-9 +/- 2%, P < 0.05, 15 mm away from injection site) and contralateral testis (-20 +/- 5%, P < 0.05). Pretreatment with 500 ng of the receptor antagonist, CGRP8-37, did not significantly attenuate the blood flow increasing affect of 50 ng CGRP, nor did 50 micrograms CGRP 8-37 (given alone) influence basal testicular blood flow in the injected testis. Using Immunohistochemistry, CGRP-containing nerves were observed in the superior and interior spermatic nerves, in the testicular artery, and in the veins leaving the testis but not in intratesticular blood vessels. CONCLUSIONS: 1) CGRP is a potent vasodilator in the testicular vasculature and it may be involved in the local regulation of testicular blood flow: 2) the testis has limited capacity to autoregulate and is consequently unable to maintain a constant testicular blood flow during large and rapid reductions in blood pressure, and 3) the local and systemic effects of vasodilators act in opposite directions in the testis.

Pituitary adenylate cyclase-activating polypeptide (PACAP): effects on blood flow in the testis and caput epididymidis of the rat.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is synthesized in developing germ cells in the testis and may act as a paracrine modulator of spermatogenesis and/or participate in tubule-interstitial interactions. Despite the abundance of PACAP in the organ, its role in testicular function has not yet been studied in vivo. Using laser Doppler flowmetry, the effects of PACAP on blood flow in the testis and caput epididymidis were studied on anesthetized adult rats. When given intratesticularly as 5- and 50-ng doses, PACAP increased blood flow by 55+/-21% (mean +/- SEM, P < 0.05) and by 68+/-11% at 5 mm from the injection site, respectively. Whereas 5 ng PACAP did not influence blood flow 15 mm from the site of injection, flow was reduced (-7+/-3; P < 0.05) at this site following treatment with 50 ng. Injection of 50 ng PACAP into the caput epididymidis increased epididymal blood flow by 18+/-4% (P < 0.05) at 1 mm from the injection site. None of the treatments above significantly affected the mean arterial blood pressure. Using immunohistochemistry, PACAP was observed in elongated spermatids and in the acrosomes of round spermatids in some, but not all, seminiferous tubules. Also, distinct PACAP immunoreactivity was seen in epithelial cells, particularly in clear cells, of the caput epididymidis. In conclusion, PACAP can induce vasodilatation in both testicular and epididymal microvessels and may be involved in regulating blood flow in these organs. Whereas the vasodilatory effect of PACAP is strong in the testis, the epididymal response appears to be more moderate.

Temporal variations in testicular microcirculation.

Temporal variations in microcirculatory blood flow in the testis and blood pressure were examined in intact, pentobarbital-anesthetized rats with a two-channel laser Doppler flowmeter. The laser Doppler probes that measure local blood flow in a tissue volume of about 2 mm3 were placed either over the mid portion of the left and right testes or on the right testes 1 cm apart. Testicular microcirculation was characterized by a prominent vasomotion with a frequency of 5.3+/-1.4 cycles per minute and with an amplitude of 73+/-32% (mean +/- SD) of the mean. In addition to this large and rapid variation in local blood flow, there were also major variations from minute to minute in the average blood flow, vasomotion frequency, and vasomotion amplitude at 40 and 53 minutes. Such variations in local blood flow, vasomotion frequency, and vasomotion amplitude were correlated with each other at two different sites on the same testis (r(s) = 0.39, r(s) = 0.82, r(s) = 0.64, respectively, P < 0.001), and they were all correlated with systemic blood pressure (r(s) 0.41, r(s) = 0.61, r(s) = 0.32, respectively, P < 0.001). Minute-to-minute variations in local blood flow, vasomotion frequency, and vasomotion amplitude were also correlated between the right and left testes (r(s) = 0.58, r(s) = 0.75, r(s) = 0.57, respectively, P < 0.001). There are substantial temporal variations in testicular microcirculation. These variations are to some extent related to temporal changes in systemic blood pressure, but changes in the ultralocal environment are probably more important. The functional significance of, and the factors responsible for, local variations in testicular microcirculation remain to be elucidated.

Effects of endothelin-1 on the rat testicular vasculature.

Endothelin-1 (ET-1), a well-known vasoconstrictor substance, is present in the testis but its functional role is unknown. The present study was undertaken to elucidate whether ET-1 may influence testicular blood flow. ET-1 (0.1, 1, 10, 100 ng), an ETA antagonist (BQ123; 0.01, 1, 100 micrograms), or saline were administered by intratesticular injections (0.1 ml) in adult rats. The effect on testicular blood flow was monitored using a laser Doppler flowmeter. The localization of immunoreactive ET-1 (irET-1) was studied by immunohistochemistry and the testicular irET-1 concentration was measured in normal and human chorionic gonadotrophin (hCG)-treated rats using a radioimmunoassay. ET-1 injection, in a dose-related way acutely decreased testicular blood flow and this effect was blocked by an ETA antagonist. The antagonist itself did not, however, influence testicular blood flow. Accumulation of polymorphonuclear leukocytes was observed in testicular venules 2 hours after ET-1 injection. Immunoreactive ET-1 was observed in Leydig, Sertoli, and endothelial cells. The testicular irET-1 content was increased 2-fold by hCG stimulation but local injection of the ET-1 antagonist did not influence testicular blood flow in hCG-treated rats. The present study suggests that ET-1 could be a hormonally regulated and locally produced modulator of testicular blood flow and microcirculation.

Unilateral injection of neuropeptide Y decreases blood flow in the injected testis but may also increase blood flow in the contralateral testis.

Neuropeptide Y (NPY) receptors have recently been described in intratesticular arterioles, but the role of NPY in testicular blood-flow regulation has not been examined. To explore this, we administered NPY in various doses (0.01-10 microg) via intratesticular injections and studied testicular microcirculation using a laser Doppler flow meter. NPY injection shows a dose-response pattern, with 1 microg (the most potent dose) causing a decrease (-42.4 +/- 3.7%, P < 0.00005) in blood flow in the ipsilateral testis of all the animals and an increase in blood flow in the contralateral testis (+17.2 +/- 5.6%, P = 0.03, n = 25 animals). The response in the contralateral testis was variable. A clear-cut increase was seen in 19 of the 25 animals examined, whereas either no response or a slight decrease was seen in the remaining six. The contralateral increase, which was not seen in the hindpaw on the same side, did not occur when the neuronal connections to the testes were blocked by injection of local anesthetics into the spermatic cord, either on the NPY-injected side or on the contralateral side. Our results suggest that NPY may serve as a vasoconstrictor in the testis, probably by acting on the NPY-Y1 receptors present on intratesticular arterioles. Local injection of NPY causes a major decrease in blood flow in the injected testis. This decrease is followed in the majority of animals studied by an increase in blood flow in the contralateral testis, an effect that seems to depend on neuronal mechanisms. This observation suggests that the testes may communicate under certain situations. The functional consequences of this remain to be elucidated.

Testicular vasomotion in different mammals.

Vasomotion is a rhythmical variation in arterial blood flow present in many different organs among them the rat testis. Vasomotion is suggested to play an important role for the transvascular fluid exchange and the exchange of nutrients over the capillary wall as well as the formation of interstitial fluid. The present study was undertaken to elucidate whether vasomotion is present in the testes of different species independent of their anatomical vascular topography. Blood flow in the testes of mouse, brush-tailed possum, tammar wallaby, ram and human was investigated by using a laser Doppler flowmeter. Vasomotion was found in all the species investigated.

Cigarette smoke and hypoxia induce acute changes in the testicular and cerebral microcirculation.

The acute effects of cigarette smoking and hypoxia on the cerebral and testicular microcirculation were studied in anestethised adult rats. Smoking for 2 min did not influence arterial pO2, pCO2 or pH but it induced an increase in cerebral blood flow by 34% and inhibited vasomotion in the testis for about 1 h. One hour after smoke exposure apnea induced a slight increase in arterial pCO2, a significant decrease in pO2, and an increase in cerebral blood flow (CBF) by 54%. In animals not previously exposed to cigarette smoke apnea increased CBF by 121%, demonstrating that a short-term exposure to tobacco smoke influences the cerebrovascular reactivity for more than one hour. In the testis, apnea resulted in a decreased blood flow by 39% and a complete depression of vasomotion. Breathing 10% O2/90% N2 resulted in moderate hypoxia, a total disappearance of the vasomotion in the testis, a 24% decrease in testicular blood flow, but a 23% increase in CBF.

Extended culture of human spermatozoa in the laboratory may have practical value in the assisted reproductive procedures.

Spermatozoa were cultured in vitro to monitor time-dependent changes in motility, viability, morphology, and membrane integrity. The degree of preservation of these clinically relevant sperm parameters over time was satisfactory. Extended culture probably can be used as a transient storage for sperm to compensate for a male's inability to produce sperm to synchronize oocyte retrieval in assisted reproduction.

Effects of haemorrhagic hypotension on the subcapsular artery and microvasculature of the rat testis.

Developing germ cells may be sensitive to even moderate reductions in blood flow. Surprisingly, however, experimental evidence suggests that the rat testis may be unable to maintain its blood flow during a decrease in systemic blood pressure. This study was therefore performed in order to answer the following questions: Is the testis able to maintain its blood flow during moderate to major reductions in blood pressure and, if so, at which level of the testicular vasculature (main artery or microcirculation) does this compensatory response take place? Moderate (-20%) and major (-40%) reductions in blood pressure were induced in anaesthetized rats by haemorrhage and the effects on testicular microvascular blood flow and subcapsular testicular artery diameter were examined by using laser Doppler flowmetry and in vivo video-microscopy respectively. Haemorrhagic hypotension led to decreased local testicular blood flow, but the relative reductions in flow were generally only half as large as the reductions in blood pressure. Hypotension also decreased the diameter of the main subcapsular testicular artery. During large reductions in blood pressure the subcapsular testicular artery constricts and testicular blood flow decreases. However, blood flow is reduced proportionally less than the mean arterial pressure, suggesting that local regulatory mechanisms are present in the testicular microvasculature, which may prevent blood flow from falling below a critical level.

Leydig cells secrete factors which increase vascular permeability and endothelial cell proliferation.

Adult intact control rats, and animals treated with human chorionic gonadotrophin (hCG) or with ethane dimethane sulphonate (EDS) to deplete Leydig cells, were injected with bromodeoxyuridine (BrdU) to label proliferating cells. Apoptotic cells were visualized by in-situ end labelling (ISEL) of fragmented DNA. Three per cent of testicular endothelial cells were labelled with BrdU and few were apoptotic in intact testes. The BrdU endothelial cell labelling index was increased by hCG-treatment and decreased in Leydig cell-depleted testes. Immunohistochemical staining showed that Leydig cells and testicular macrophages contain immunoreactive vascular endothelial growth factor (irVEGF). The ability of testicular cells to stimulate angiogenesis was studied further by transplanting interstitial cells or seminiferous tubule segments under the kidney capsule. A prominent vascular network was observed around interstitial cell grafts, but not around tubule grafts. Treatment of transplanted rats with human chorionic gonadotrophin (hCG, 50 i.u.) resulted in an accumulation of PMN-leukocytes and an increase in vascular permeability in the remaining testis and in interstitial cell grafts. Interstitial cells from Leydig cell-depleted (EDS-treated) testes were also transplanted under the kidney capsule. This type of graft caused only a discrete stimulation of angiogenesis, and there was no increase in vascular permeability around the graft after hCG treatment. It is suggested that Leydig cells secrete angiogenic factors and that they are the source of the inflammation mediator(s) produced in the testis after hCG treatment. The high proliferation rate in endothelial cells suggests continuous remodelling of the testicular microvasculature, but the functional significance of this remains unknown.

Tobacco smoke disrupts testicular microcirculation in the rat.

Anaesthetized adult rats were exposed repeatedly to cigarette smoke for 2 s interspersed with exposure to fresh air for either 10, 15 or 30 s using a smoking apparatus. The acute effects of this treatment on testicular microcirculation were studied using laser Doppler flowmetry. Peripheral tissue O2 saturation was measured continuously in the foot during the experiment. Exposure to cigarette smoke caused a moderate acute increase in the testicular blood flow and it inhibited vasomotion. Blood flow and the pattern of vasomotion were normalized after termination of smoke exposure. The time between the last smoke exposure and flow normalization was dependent on the smoke/air dose. Peripheral tissue O2 saturation did not change during the experiments. The effects on testicular microcirculation of local injections of an aqueous extract of cigarette smoke and passive smoking were also studied. Local injection of smoke extract increased blood flow and inhibited vasomotion. Passive smoking caused a moderate decrease in the frequency of vasomotion and amplitude. The observation that cigarette smoke influences testicular microcirculation acutely is discussed in relation to possible adverse effects on spermatogenesis.

Atrial natriuretic peptide, brain natriuretic peptide and c-type natriuretic peptide: effects on testicular microcirculation and immunohistochemical localization.

The effect of local injection of atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides and an ANP antagonist (HS-142-1) on testicular microcirculation and vasomotion was studied using laser Doppler flowmetry. The natriuretic peptides were also localized immunohistochemically within the testis. ANP, BNP-32, CNP-22 and CNP-53 all caused a dose-related increase in testicular blood flow. The effect of ANP was blocked by concomitant injection of the ANP antagonist. Immunoreactive (ir) CNP and ir BNP were found in Leydig cells whereas in ANP was observed in the seminiferous tubules. It is suggested that the natriuretic peptides could play a role in local regulation of the testicular microcirculation.

Effects of acute graded reductions in testicular blood flow on testicular morphology in the adult rat.

The effect of moderate reductions in testicular blood flow has not been studied systematically. The aim of this study was, therefore, to examine the effects of different degrees of blood flow reduction on testicular morphology and to determine how much flow can be reduced before damage occurs. The subcapsular testicular artery was partially ligated in the left testes of adult rats. Testicular blood flow was measured before, immediately after, and 5 h after the ligation using laser Doppler flowmetry. After 5 h of partial ligation, the testes were removed, and their morphology was examined and related to the degree of blood flow reduction. The number of in situ end-labeled- or TUNEL-positive (i.e., dying) germ cells and the volume density of intravascular polymorphonuclear (PMN) leukocytes were measured. When flow was reduced to approximately 70% or less of its pretreatment value, a dose-related increase in the number of dying spermatogonia and early spermatocytes was seen. The PMN leukocytes accumulated in testicular blood vessels after partial ligation, and the maximum number was observed in testes where flow was reduced by approximately 50% of the pretreatment value. In conclusion, early stages of spermatogenesis are sensitive to a moderate, acute reduction in blood flow. Discrete reductions in flow may, therefore, have a large impact on sperm production.

Is nitric oxide involved in the regulation of the rat testicular vasculature?

Using immunohistochemistry, endothelial nitric oxide synthase (NOS), and neuronal NOS were localized in the endothelium of rat testicular arteries and in Leydig cells, respectively. NADPH-diaphorase activity, indicating NOS activity, however, was present only in endothelial cells. In order to examine the role of nitric oxide (NO) in the regulation of rat testicular vasculature, intact and hCG-pretreated (50-100 IU hCG given s.c. 6 h earlier) animals were given injections of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg i.v.). In all rats this resulted in a major increase in blood pressure. In intact, unstimulated animals, testicular vascular resistance was unaffected, and testicular blood flow consequently increased. In hCG-treated animals, in contrast, vascular resistance increased in an hCG dose-related way. L-NAME treatment also increased the hCG-induced accumulation of polymorphonuclear leukocytes in testicular venules. Treatment with N(G)-nitro-D-arginine methyl ester (D-NAME, 10 mg/kg i.v.), an inactive isomer of L-NAME, had no effect on the testicular vasculature. The study suggests that NO plays only a limited role in the regulation of testicular blood flow under basal conditions. After hCG treatment, however, NOS activity appears to be increased (increased endothelial NADPH-diaphorase staining), suggesting that NO in this situation is of importance to increase blood flow and to inhibit leukocyte accumulation.