Abstract-The balance between endothelial nitric oxide (NO) and angiotensin II (Ang II) maintains the homeostasis of the cardiovascular and renal systems. We tested the hypothesis that increased oxidant stress linked to a functional imbalance between NO and Ang II might play a central pathogenetic role in salt-sensitive (SS) hypertension. We studied Dahl SS (DS) rats during the prehypertensive (5 days) and hypertensive (12 weeks) phases of a high-salt (4% NaCl) diet. Control rats received a normal-salt (0.5% NaCl, Key Words: angiotensin II Ⅲ endothelium Ⅲ nitric oxide Ⅲ oxidative stress Ⅲ hypertension, sodium-dependent E xtensive studies of the relation between salt and blood pressure have established that some individuals are sensitive to dietary salt changes, whereas others are resistant. 1 Epidemiologically, salt sensitivity (SS) affects Ϸ50% of hypertensive patients and 20% of normotensive patients. 2 SS hypertensive patients almost uniformly have low plasma renin levels and often manifest microalbuminuria. 3 SS hypertension, which is more prevalent in blacks and the elderly, has traditionally been considered a "volume-dependent hypertension," in which the role of angiotensin II (Ang II) was presumed to be irrelevant because of suppressed plasma renin. 4 However, recent studies in Dahl SS (DS) rats, a well-known model of SS hypertension, have suggested that SS hypertension is accompanied by increased activation of the local renal renin-angiotensin system. 5-7 On the basis of these studies, we hypothesize that functional upregulation of the renin-angiotensin system linked to a concomitant decrease in the bioactivity of nitric oxide (NO) might be an important contributor to the pathophysiology of endothelial dysfunction and end-organ injury in SS hypertension. 8 -10 There is an antagonistic interaction between endothelial NO and Ang II, 11-13 and the balance between NO and Ang II appears crucial for maintaining homeostasis of the cardiovascular and renal systems, 13 particularly for regulation of vascular tone and modulation of growth-related pathologic changes. 14 The functional interaction is such that a reduction in NO bioactivity represents a proportional increment in the bioactivity of Ang II. 15 Furthermore, recent studies have reported that long-term inhibition of NO synthesis actually results in upregulation of the synthesis of Ang II, as well as expression of the Ang II type 1 (AT 1 ) receptor. 16 Ang II activates NADH/NADPH oxidase in endothelial cells, vascular smooth muscle cells, adventitial fibroblasts, and glomerular mesangial cells. 17-20 NADH/NADPH oxidase in turn produces superoxide anion (O 2 -), which avidly interacts with NO, reduces its bioactivity, and generates peroxynitrite. [21][22][23] Elegant studies in patients with renovascular hypertension 24 as well as ex vivo studies of human arteries have demonstrated that the biologic interaction between Ang II, O 2 -, and NO is fully operative in humans. 25
Abstract. Experimental renal scarring indicates that tissue transglutaminase (tTg) may be associated with the accumulation of extracellular matrix (ECM), both indirectly via TGF-1 activation and directly by the formation of ⑀(␥-glutamyl) lysine dipeptide bonds within the ECM. The latter potentially accelerates deposition and confers the ECM with resistance to proteolytic digestion. Studied were 136 human renal biopsy samples from a range of chronic renal diseases (CRD) to determine changes in tTg and ⑀(␥-glutamyl) lysine crosslinking. Immunofluorescence for insoluble tTg showed a 14-fold increase in the kidneys of CRD patients (5.3 Ϯ 0.5 versus 76 Ϯ 54 mV/cm 2 ), which was shown to be active by a similar 11-fold increase in the ⑀(␥-glutamyl) lysine crosslink (1.8 Ϯ 0.2 versus 19.3 Ϯ 14.2 mV/cm 2 ). Correlations were obtained with renal function for tTg and crosslink. In situ hybridization for tTg mRNA showed that tubular epithelial cells were the major source of tTg; however, both mesangial and interstitial cells also contributed to elevated levels in CRD. This mRNA pattern was consistent with immunohistochemistry for soluble tTg. Changes in renal tTg and its product, the ⑀(␥-glutamyl) lysine crosslink, occur in progressive renal scarring in humans independently of the original etiology and in a similar manner to experimental models. tTg may therefore play a role in the pathogenesis of renal scarring and fibrosis in patients with CRD and can therefore be considered a potential therapeutic target.
ObjectiveCardiovascular disease (CVD) is one of the leading non-AIDS-defining causes of death among HIV-positive (HIV+) individuals. However, the evidence surrounding specific components of CVD risk remains inconclusive. We conducted a systematic review and meta-analysis to synthesise the available evidence and establish the risk of myocardial infarction (MI) among HIV+ compared with uninfected individuals. We also examined MI risk within subgroups of HIV+ individuals according to exposure to combination antiretroviral therapy (ART), ART class/regimen, CD4 cell count and plasma viral load (pVL) levels.DesignSystematic review and meta-analysis.Data sourcesWe searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews until 18 July 2018. Furthermore, we scanned recent HIV conference abstracts (CROI, IAS/AIDS) and bibliographies of relevant articles.Eligibility criteriaOriginal studies published after December 1999 and reporting comparative data relating to the rate of MI among HIV+ individuals were included.Data extraction and synthesisTwo reviewers working in duplicate, independently extracted data. Data were pooled using random-effects meta-analysis and reported as relative risk (RR) with 95% CI.ResultsThirty-two of the 8130 identified records were included in the review. The pooled RR suggests that HIV+ individuals have a greater risk of MI compared with uninfected individuals (RR: 1.73; 95% CI 1.44 to 2.08). Depending on risk stratification, there was moderate variation according to ART uptake (RR, ART-treated=1.80; 95% CI 1.17 to 2.77; ART-untreated HIV+ individuals: 1.25; 95% CI 0.93 to 1.67, both relative to uninfected individuals). We found low CD4 count, high pVL and certain ART characteristics including cumulative ART exposure, any/cumulative use of protease inhibitors as a class, and exposure to specific ART drugs (eg, abacavir) to be importantly associated with a greater MI risk.ConclusionsOur results indicate that HIV infection, low CD4, high pVL, cumulative ART use in general including certain exposure to specific ART class/regimen are associated with increased risk of MI. The association with cumulative ART may be an index of the duration of HIV infection with its attendant inflammation, and not entirely the effect of cumulative exposure to ART per se.PROSPERO registration numberCRD42014012977.
BackgroundThere is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmesMethods(i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation.Results(i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1), male gender (aOR 1.89, 95% C.I. 1.39–2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07–1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function.ConclusionIn this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited.
MCs as an infiltrating hematopoietic cell and its growth factor (SCF) seem to be up-regulated in glomerulonephritis, and may play a role in the development of renal fibrosis.
Testicular torsion is a challenging and time-sensitive diagnosis that is encountered frequently in daily practice, especially in the emergency room. A thorough history, the presence of a painful and swollen testis and testicular ultrasonography plays a vital role in the prompt diagnosis of testicular torsion. Prompt diagnosis is essential to prevent complications of testicular torsion which include testicular infarction, necrosis, and sub/infertility. This can be challenging as there are various other conditions that may mimic the presentation of testicular torsion. Since testicular torsion is an extremely time-sensitive diagnosis, it may also be a subject of many medicolegal challenges. This review article serves as a guide for clinicians involved with the diagnosis and management of testicular torsion. We review and discuss detection and management strategies based on their validity, statistical significance, and effectiveness in enabling prompt diagnosis and management of testicular torsion. Medicolegal implications of testicular torsion are also highlighted.
The current PCa risk calculator mobile Apps available may be beneficial in counselling the concerned at risk patient. These Apps have potential to assist both the patient and the urologist alike. The PCa risk calculator App 'predictability' may be further enhanced by the incorporation of newly validated risk factors and predictors for PCa.
The WS, when correctly diagnosed, may be viewed as a very definitive sign for TT in the pediatric and adult populations. However, its role in neonates is limited.
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