Isolated Nocturnal Hypertension in People Living With Human Immunodeficiency Virus: A Cross-Sectional Study.

BACKGROUND: Nocturnal hypertension (NH) is a potent cardiovascular risk factor described frequently in people with HIV (PWH). Isolated NH (INH) is less well reported in PWH because of the need for ambulatory blood pressure monitoring (ABPM) in office normotensive patients. We aim to document the prevalence of NH and INH and the clinical factors associated with these phenotypes. METHODS: Cross-sectional study from an HIV program in Argentina. Office and ABPM measurements, as well as clinical and laboratory exploration, were performed. We defined INH as NH with daytime normotension in patients with office normotension. RESULTS: We obtained ABPM in 66 PWH, 60% male, aged 44.7 (IQR 27-69) years; 87% receiving antiretroviral therapy, and 86.2% virologically suppressed. ABPM-based hypertension prevalence was 54.7% (95% CI: 42.5-66.3). The prevalence of NH was 48.5% (32/66), while the INH prevalence was 19.7% (95% CI: 11.7-30.9). No differences were found regarding sex, HIV viral load, CD4+ T lymphocytes count, or years of infection between normotensive and INH patients. Multiple linear regression model adjusted for sex and age determined that body mass index (ß = 0.93, P < 0.01), plasma uric acid (ß = 0.25, P = 0.04), plasma potassium (ß = -10.1, P = 0.01), and high-sensitivity C-reactive protein (hs-CRP) (ß = 0.78, P = 0.02) independently predicted nocturnal systolic blood pressure (BP) in PWH. In a multiple logistic regression model adjusted for age and sex, the presence of sedentariness, plasma potassium <4 mEq/L, BMI, and hs-CRP levels were predictors of INH. CONCLUSION: INH is highly prevalent in PWH. Metabolic and inflammatory markers predict nocturnal SBP in PWH.

Social determinants of blood pressure control in a middle-income country in Latin America.

Blood pressure (BP) control is a key intervention to decrease cardiovascular diseases (CVD), the main cause of death in low and middle-income countries (MIC). Scarce data on the determinants of BP control in Latin America are available. Our objective is to explore the role of gender, age, education, and income as social determinants of BP control in Argentina, a MIC with a universal health care system. We evaluated 1184 persons in two hospitals. Blood pressure was measured using automatic oscillometric devices. We selected those patients treated for hypertension. The average BP of less than 140/90 mmHg was considered a controlled BP. We found 638 hypertensive individuals, of whom 477 (75%) were receiving antihypertensive drugs, and of those, 248 (52%) had controlled BP. The prevalence of low education was more frequent in uncontrolled patients (25.3% vs. 16.1%; P < .01). We did not find association between household income, gender, and BP control. Older patients had less BP control (44% of those older than 75 years vs. 60.9% of those younger than 40; test for trend P < .05). Multivariate regression indicates low education (OR 1.71 95% CI [1.05, 2.79]; P = .03) and older age (OR 1.01; 95% IC [1.00, 1.03]) as independent predictors of the lack of BP control. We conclude that rates of BP control are low in Argentina. In a MIC with a universal health care system low education and old age but not household income are independent predictors of the lack of BP control.

Epithelial N-methyl-D-aspartate (NMDA) receptors mediate renal vasodilation by affecting kidney autoregulation.

Background: N-methyl-D-aspartate receptor (NMDAR) are amino acid receptors that are well studied in brain physiology; however, their role in kidney is poorly understood. Nonetheless, NMDAR inhibitors can increase serum K+ and reduce GFR, which suggests they have an important physiological role in the kidney. We hypothesized that NMDARs in the distal nephron induce afferent-arteriole vasodilation through the vasodilator mechanism connecting-tubule-glomerular feedback (CNTGF) that involves ENaC activation. Methods and results: Using a tubule-specific transcriptome database combined with molecular biology and microscopy techniques, we showed kidney expression of NMDAR subunits along the nephron and specifically in ENaC-positive cells. This receptor is expressed in both male and female mice, with higher abundance in females (p=0.02). Microperfusing NMDAR agonists into the connecting tubule induced afferent-arteriole vasodilation (EC50 10.7 vs. 24.5 mM; p<0.001) that was blunted or eliminated with the use of NMDAR blocker MK-801 or with the ENaC inhibitor Benzamil, indicating a dependence on CNTGF of the NMDAR-induced vasodilation. In vivo, we confirmed this CNTGF-associated vasodilation using kidney micropuncture (Stop-flow pressure 37.9±2.6 vs. 28.6±1.9 mmHg, NMDAR agonist vs vehicle; p<0.01). We explored NMDAR and ENaC channel interaction by using mpkCCD cells and split-open connecting tubules. We observed increased amiloride-sensitive current following NMDAR activation that was prevented by MK-801 (1.14 vs. 0.4 µAmp; p=0.03). In split-open tubules, NMDAR activation increased ENaC activity (Npo Vehicle vs. NMDA; p=0.04). Conclusion: NMDARs are expressed along the nephron, including ENaC-positive cells, with higher expression in females. Epithelial NMDAR mediates renal vasodilation through the connecting-tubule-glomerular feedback, by increasing ENaC activity.

Global blood pressure screening during the COVID-19 pandemic: results from the May Measurement Month 2021 campaign.

BACKGROUND: Raised blood pressure (BP) remains the biggest risk factor contributing to the global burden of disease and mortality, despite the COVID-19 pandemic. May Measurement Month (MMM), an annual global screening campaign aims to highlight the importance of BP measurement by evaluating global awareness, treatment and control rates among adults with hypertension. In 2021, we assessed the global burden of these rates during the COVID-19 pandemic. METHODS: Screening sites were set up in 54 countries between May and November 2021 and screenees were recruited by convenience sampling. Three sitting BPs were measured, and a questionnaire completed including demographic, lifestyle and clinical data. Hypertension was defined as a systolic BP at least 140 mmHg and/or a diastolic BP at least 90 mmHg (using the mean of the second and third readings) or taking antihypertensive medication. Multiple imputation was used to impute the average BP when readings were missing. RESULTS: Of the 642 057 screenees, 225 882 (35.2%) were classified as hypertensive, of whom 56.8% were aware, and 50.3% were on antihypertensive medication. Of those on treatment, 53.9% had controlled BP (<140/90 mmHg). Awareness, treatment and control rates were lower than those reported in MMM campaigns before the COVID-19 pandemic. Minimal changes were apparent among those testing positive for, or being vaccinated against COVID-19. Of those on antihypertensive medication, 94.7% reported no change in their treatment because of the COVID-19 pandemic. CONCLUSION: The high yield of untreated or inadequately treated hypertension in MMM 2021 confirms the need for systematic BP screening where it does not currently exist.

Addressing global disparities in blood pressure control: perspectives of the International Society of Hypertension.

ABSTRACT: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework.

Is Isolated Diastolic Hypertension an Important Phenotype?

PURPOSE OF REVIEW: Isolated diastolic hypertension (IDH) is a frequent hypertension phenotype. We review IDH pathophysiology, risk stratification, and therapeutic decisions. RECENT FINDINGS: Recent guidelines lowering blood pressure cutoff levels have increased IDH prevalence and likely decreased associated cardiovascular risk. Long-term cardiovascular risk and pharmacological intervention in IDH are controversial. Narrow pulse pressure and other physiological and epidemiological characteristics are shared with a systodiastolic hypertension (SDH) subgroup. We propose that IDH be incorporated into a broader category, predominantly diastolic hypertension (PDH), defined by pulse pressure ≤ 45 mmHg and includes IDH and SDH with a narrow pulse pressure. IDH-PDH is associated with cardiovascular risk in the long term, especially in young patients. Standardization of the IDH definition and population may contribute to future research to understand genetics, pathophysiology, and eventually therapy in this important subgroup of hypertensive patients.

[Hypertension and metabolic syndrome in HIV infected patients]. / Hipertensión y síndrome metabólico en pacientes con virus de la inmunodeficiencia-humana.

Cardiovascular diseases (CVD) are a growing cause of mortality between human immunodeficiency virus (HIV) infected patients. Hypertension (HTN) and metabolic syndrome (MS) are important causes of CVD. The prevalence of HTN and MS in HIV infected patients in Córdoba, Argentina is unknown. Our aim is to determine the prevalence of HTN and MS in HIV patients in Córdoba and their association with immunological state, inflammation and highly active antiretroviral therapy (HAART) in an observational study. Sixty-five HIV infected patients from the provincial HIV program were randomly selected. Fifty-seven (87%) were on HAART, 39 (60%) were males. The mean age was 44.7 ± 10 years. Mean CD4+ T lymphocytes (CD4+T) count was 404.4 ± 289.6 cells/ml. Viral load (VL) was undetectable in 56 (86.2%). The prevalence of HTN was 40%, and it was associated with the duration of HAART (p < 0.05). There was no association between years of HIV infection, CD4+T, VL and blood pressure. The prevalence of MS was 38.5% (25/65). MS was more frequent between those with HAART (OR: 1.80; CI 95%; 1.43-2.28; p = 0.02). Patients on HAART had higher rates of hypertriglyceridemia, impaired glucose tolerance and lower levels of HDLc (p < 0.01). MS was associated with the HAART duration (p < 0.01). HIV infected patients had a high prevalence of HTN and MS. HAART was associated with both HTN and MS, but there was no association between immunological status, VL or inflammatory markers.

La enfermedad cardiovascular y sus factores de riesgos como hipertensión arterial (HTA) y síndrome metabólico (SM), son una creciente causa de mortalidad entre los infectados con HIV. Nuestros objetivos fueron determinar la prevalencia HTA y SM en pacientes HIV positivos de la ciudad de Córdoba su asociación con el estado inmunológico, inflamación y terapia antirretroviral (TARAA). Fue un estudio aleatorizado de corte transversal. Se incluyeron 65 pacientes HIV positivos del programa provincial HIV-Córdoba, 57 (87%) recibían TARAA, 39 (60%) eran masculinos, con edad promedio de 44.7 ± 10 años. La concentración de linfocitos T CD4+ (LTCD4+) fue 404.4 ± 289.6 cel./ml. La carga viral (CV) fue indetectable en 56 (86.2%). La prevalencia de HTA fue de 40% (26/65) y se asoció a la duración de TARAA (p < 0.05). No hubo asociación entre años de infección por HIV, LTCD4+ y CV con HTA. La prevalencia de SM fue de 38.5% (25/65). El uso de TARAA fue más frecuente en aquellos con SM (OR: 1.80; IC95%: 1.43-2.28; p = 0.02). Pacientes bajo TARAA presentaron alta tasa de hipertrigliceridemia, intolerancia a la glucosa y niveles bajos de HDL (todos p < 0.01). SM se asoció a la duración de TARAA (p < 0.01). La TARAA se asoció a HTA y SM, no encontrándose relación con estado inmunológico, CV o marcadores de inflamación.

Hipertensión y síndrome metabólico en pacientes con Virus de la Inmunodeficiencia-Humana / Hypertension and metabolic syndrome in HIV infected patients

Resumen La enfermedad cardiovascular y sus factores de riesgos como hipertensión arterial (HTA) y síndrome metabólico (SM), son una creciente causa de mortalidad entre los infectados con HIV. Nuestros objetivos fueron determinar la prevalencia HTA y SM en pacientes HIV positivos de la ciudad de Córdoba su asociación con el estado inmunológico, inflamación y terapia antirretroviral (TARAA). Fue un estudio aleatorizado de corte transversal. Se incluyeron 65 pacientes HIV positivos del programa provincial HIV-Córdoba, 57 (87%) recibían TARAA, 39 (60%) eran masculinos, con edad promedio de 44.7 ± 10 años. La concentración de linfocitos T CD4+ (LTCD4+) fue 404.4 ± 289.6 cel./ml. La carga viral (CV) fue indetectable en 56 (86.2%). La prevalencia de HTA fue de 40% (26/65) y se asoció a la duración de TARAA (p < 0.05). No hubo asociación entre años de infección por HIV, LTCD4+ y CV con HTA. La prevalencia de SM fue de 38.5% (25/65). El uso de TARAA fue más frecuente en aquellos con SM (OR: 1.80; IC95%: 1.43-2.28; p = 0.02). Pacientes bajo TARAA presentaron alta tasa de hipertrigliceridemia, intolerancia a la glucosa y niveles bajos de HDL (todos p < 0.01). SM se asoció a la duración de TARAA (p < 0.01). La TARAA se asoció a HTA y SM, no encontrándose relación con estado inmunológico, CV o marcadores de inflamación.

Abstract Cardiovascular diseases (CVD) are a growing cause of mortality between human immunodeficiency virus (HIV) infected patients. Hypertension (HTN) and metabolic syndrome (MS) are important causes of CVD. The prevalence of HTN and MS in HIV infected patients in Córdoba, Argentina is unknown. Our aim is to determine the prevalence of HTN and MS in HIV patients in Córdoba and their association with immunological state, inflammation and highly active antiretroviral therapy (HAART) in an observational study. Sixty-five HIV infected patients from the provincial HIV program were randomly selected. Fifty-seven (87%) were on HAART, 39 (60%) were males. The mean age was 44.7 ± 10 years. Mean CD4+ T lymphocytes (CD4+T) count was 404.4 ± 289.6 cells/ml. Viral load (VL) was undetectable in 56 (86.2%). The prevalence of HTN was 40%, and it was associated with the duration of HAART (p < 0.05). There was no association between years of HIV infection, CD4+T, VL and blood pressure. The prevalence of MS was 38.5% (25/65). MS was more frequent between those with HAART (OR: 1.80; CI 95%; 1.43-2.28; p = 0.02). Patients on HAART had higher rates of hypertriglyceridemia, impaired glucose tolerance and lower levels of HDLc (p < 0.01). MS was associated with the HAART duration (p < 0.01). HIV infected patients had a high prevalence of HTN and MS. HAART was associated with both HTN and MS, but there was no association between immunological status, VL or inflammatory markers.

The Renal Physiology of Pendrin-Positive Intercalated Cells.

Intercalated cells (ICs) are found in the connecting tubule and the collecting duct. Of the three IC subtypes identified, type B intercalated cells are one of the best characterized and known to mediate Cl- absorption and HCO3- secretion, largely through the anion exchanger pendrin. This exchanger is thought to act in tandem with the Na+-dependent Cl-/HCO3- exchanger, NDCBE, to mediate net NaCl absorption. Pendrin is stimulated by angiotensin II and aldosterone administration via the angiotensin type 1a and the mineralocorticoid receptors, respectively. It is also stimulated in models of metabolic alkalosis, such as with NaHCO3 administration. In some rodent models, pendrin-mediated HCO3- secretion modulates acid-base balance. However, of probably more physiological or clinical significance is the role of these pendrin-positive ICs in blood pressure regulation, which occurs, at least in part, through pendrin-mediated renal Cl- absorption, as well as their effect on the epithelial Na+ channel, ENaC. Aldosterone stimulates ENaC directly through principal cell mineralocorticoid hormone receptor (ligand) binding and also indirectly through its effect on pendrin expression and function. In so doing, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. In addition to its role in Na+ and Cl- balance, pendrin affects the balance of other ions, such as K+ and I-. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contribution of pendrin-positive ICs in the kidney to distal nephron function and blood pressure.

Aldosterone Regulates Pendrin and Epithelial Sodium Channel Activity through Intercalated Cell Mineralocorticoid Receptor-Dependent and -Independent Mechanisms over a Wide Range in Serum Potassium.

BACKGROUND: Aldosterone activates the intercalated cell mineralocorticoid receptor, which is enhanced with hypokalemia. Whether this receptor directly regulates the intercalated cell chloride/bicarbonate exchanger pendrin is unclear, as are potassium's role in this response and the receptor's effect on intercalated and principal cell function in the cortical collecting duct (CCD). METHODS: We measured CCD chloride absorption, transepithelial voltage, epithelial sodium channel activity, and pendrin abundance and subcellular distribution in wild-type and intercalated cell-specific mineralocorticoid receptor knockout mice. To determine if the receptor directly regulates pendrin, as well as the effect of serum aldosterone and potassium on this response, we measured pendrin label intensity and subcellular distribution in wild-type mice, knockout mice, and receptor-positive and receptor-negative intercalated cells from the same knockout mice. RESULTS: Ablation of the intercalated cell mineralocorticoid receptor in CCDs from aldosterone-treated mice reduced chloride absorption and epithelial sodium channel activity, despite principal cell mineralocorticoid receptor expression in the knockout mice. With high circulating aldosterone, intercalated cell mineralocorticoid receptor gene ablation directly reduced pendrin's relative abundance in the apical membrane region and pendrin abundance per cell whether serum potassium was high or low. Intercalated cell mineralocorticoid receptor ablation blunted, but did not eliminate, aldosterone's effect on pendrin total and apical abundance and subcellular distribution. CONCLUSIONS: With high circulating aldosterone, intercalated cell mineralocorticoid receptor ablation reduces chloride absorption in the CCD and indirectly reduces principal cell epithelial sodium channel abundance and function. This receptor directly regulates pendrin's total abundance and its relative abundance in the apical membrane region over a wide range in serum potassium concentration. Aldosterone regulates pendrin through mechanisms both dependent and independent of the IC MR receptor.

Blood Pressure Screening Campaign in Jamaica: May Measurement Month 2017.

BACKGROUND: Hypertension (HTN) is responsible for a significant disease burden in Jamaica. We are reporting the results of the 2017 blood pressure (BP) screening campaign May Measurement Month in Jamaica that aimed to increase the awareness of HTN. METHODS: Adults, 18 years old and older, from different parishes of Jamaica were invited to participate during May to June 2017. Demographic data were collected. BP, weight, and height were measured and recorded. RESULTS: Five hundred sixty-six participants (n = 566) were enrolled, 91.6% (519) from urban areas, and 72.6% (410) were females. The average age was 53.7 (18-95) years old and body mass index was 28.2 ± 6.6 kg/m2. The prevalence of HTN was 47.3% (267/566), without gender or living areas differences (both P > 0.1). Prevalence of HTN was lower in those who self-identified as Interracial ethnicity, in comparison with Afro-Caribbean (33% vs. 48.3%; P = 0.04). About third of the hypertensive patients were not aware of the high BP (89/267; 35.6%). Between hypertensive patients, 64.4% (172/267) were receiving antihypertensive drugs. The rate of BP control was 32% of the hypertensive patients and 50% of those receiving antihypertensive medication. Significant lower BP control was observed between diabetic vs. nondiabetic patients (34.3% vs. 60%; P < 0.001). CONCLUSION: We found a high prevalence of HTN in this population, especially in patients with diabetes or previous cardiovascular diseases. We report an increase in HTN awareness in Jamaica but more advances need to be performed to increase HTN treatment and control.

May Measurement Month 2017: analysis of the blood pressure screening results in Argentina-Americas.

Hypertension is a growing concern worldwide, causing over 10 million deaths each year. The prevalence of high blood pressure (BP) in Argentina is 36.3% and 38% of these are unaware of their disease. Half of the hypertensive patients are on pharmacological treatment and only a quarter of them are controlled. The International Society of Hypertension initiated the May Measurement Month (MMM) as a global campaign to raise awareness on high BP that may also serve as a temporary solution to the lack of global screening programs worldwide. A volunteer cross-sectional survey was carried out in May 2017 across 56 health centres. Blood pressure measurement, definition of hypertension and statistical analysis followed the MMM protocol. For this awareness campaign, the Argentine Society of Hypertension coined the slogan: 'Know and control your blood pressure'. A total of 32 346 individuals aged at least 18 years were screened during MMM17. After imputation, 16 263 (50.4%) were hypertensive. Of the 12 156 receiving antihypertensive medication 5400 (44.4%) still had uncontrolled BP. MMM17, called in our country 'Know and control your blood pressure', was the largest BP screening campaign done in Argentina. Almost 6 out of 10 hypertensive patients were either not on treatment or were not controlled to the BP goal. These results suggest that appropriate screening can help to identify a significant number of people with high BP.

Tubule-vascular feedback in renal autoregulation.

Afferent arteriole (Af-Art) diameter regulates pressure and flow into the glomerulus, which are the main determinants of the glomerular filtration rate. Thus, Af-Art resistance is crucial for Na+ filtration. Af-Arts play a role as integrative centers, where systemic and local systems interact to determine the final degree of resistance. The tubule of a single nephron contacts an Af-Art of the same nephron at two locations: in the transition of the thick ascending limb to the distal tubule (macula densa) and again in the connecting tubule. These two sites are the anatomic basis of two intrinsic feedback mechanisms: tubule-glomerular feedback and connecting tubule-glomerular feedback. The cross communications between the tubules and Af-Arts integrate tubular Na+ and water processing with the hemodynamic conditions of the kidneys. Tubule-glomerular feedback provides negative feedback that tends to avoid salt loss, and connecting tubule-glomerular feedback provides positive feedback that favors salt excretion by modulating tubule-glomerular feedback (resetting it) and increasing glomerular filtration rate. These feedback mechanisms are also exposed to systemic modulators (hormones and the nervous system); however, they can work in isolated kidneys or nephrons. The exaggerated activation or absence of any of these mechanisms may lead to disequilibrium in salt and water homeostasis, especially in extreme conditions (e.g., high-salt diet/low-salt diet) and may be part of the pathogenesis of some diseases. In this review, we focus on molecular signaling, feedback interactions, and the physiological roles of these two feedback mechanisms.

A Novel Mechanism of Renal Microcirculation Regulation: Connecting Tubule-Glomerular Feedback.

PURPOSE OF REVIEW: In this review, we summarized the current knowledge of connecting tubule-glomerular feedback (CTGF), a novel mechanism of renal microcirculation regulation that integrates sodium handling in the connecting tubule (CNT) with kidney hemodynamics. RECENT FINDINGS: Connecting tubule-glomerular feedback is a crosstalk communication between the CNT and the afferent arteriole (Af-Art), initiated by sodium chloride through the epithelial sodium channel (ENaC). High sodium in the CNT induces Af-Art vasodilation, increasing glomerular pressure and the glomerular filtration rate and favoring sodium excretion. CTGF antagonized and reset tubuloglomerular feedback and thus increased sodium excretion. CTGF is absent in spontaneous hypertensive rats and is overactivated in Dahl salt-sensitive rats. CTGF is also modulated by angiotensin II and aldosterone. CTGF is a feedback mechanism that integrates sodium handling in the CNT with glomerular hemodynamics. Lack of CTGF could promote hypertension, and CTGF overactivation may favor glomerular damage and proteinuria. More studies are needed to explore the alterations in renal microcirculation and the role of these alterations in the genesis of hypertension and glomerular damage in animals and humans. KEY POINTS: • CTGF is a vasodilator mechanism that regulates afferent arteriole resistance. • CTGF is absent in spontaneous hypertensive rats and overactivated in Dahl salt-sensitive rats. • CTGF in excess may promote glomerular damage and proteinuria, while the absence may participate in sodium retention and hypertension.

Renal release of N-acetyl-seryl-aspartyl-lysyl-proline is part of an antifibrotic peptidergic system in the kidney.

The antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is released from thymosin-ß4 (Tß4) by the meprin-α and prolyl oligopeptidase (POP) enzymes and is hydrolyzed by angiotensin-converting enzyme (ACE). Ac-SDKP is present in urine; however, it is not clear whether de novo tubular release occurs or if glomerular filtration is the main source. We hypothesized that Ac-SDKP is released into the lumen of the nephrons and that it exerts an antifibrotic effect. We determined the presence of Tß4, meprin-α, and POP in the kidneys of Sprague-Dawley rats. The stop-flow technique was used to evaluate Ac-SDKP formation in different nephron segments. Finally, we decreased Ac-SDKP formation by inhibiting the POP enzyme and evaluated the long-term effect in renal fibrosis. The Tß4 precursor and the releasing enzymes meprin-α and POP were expressed in the kidneys. POP enzyme activity was almost double that in the renal medulla compared with the renal cortex. With the use of the stop-flow technique, we detected the highest Ac-SDKP concentrations in the distal nephron. The infusion of a POP inhibitor into the kidney decreased the amount of Ac-SDKP in distal nephron segments and in the proximal nephron to a minor extent. An ACE inhibitor increased the Ac-SDKP content in all nephron segments, but the increase was highest in the distal portion. The chronic infusion of a POP inhibitor increased kidney medullary fibrosis, which was prevented by Ac-SDKP. We conclude that Ac-SDKP is released by the nephron and is part of an important antifibrotic system in the kidney.

Oral vitamin D3 5000 IU/day as an adjuvant in the treatment of atopic dermatitis: a randomized control trial.

BACKGROUND: Vitamin D has immunomodulatory effects both in the innate and adaptive immune systems, and there is growing scientific evidence demonstrating its relevance in inflammatory processes such as AD. HYPOTHESIS: If vitamin D3 promotes the skin immune system, then it should improve the response to treatment of patients with AD. METHODS: A randomized, double-blind placebo-controlled clinical trial was conducted, which included 65 patients with AD according to Hanifin-Rajka criteria and the severity scale (SCORAD). The patients were divided into two groups to receive either vitamin D3 5000 IU/day (n = 33) or placebo (n = 32), plus baseline therapy (topical steroid, soap substitute, and emollient) during 3 months. RESULTS: Fifty-eight of the 65 enrolled subjects were included in the analysis. At the end of the intervention, the treated group achieved higher levels of 25(OH)D (P < 0.001). At week 12, those patients who registered serum levels of 25(OH)D ≥20 ng/ml, regardless of whether or not they had received supplementation, showed a lower SCORAD compared to those with levels <20 ng/ml (P < 0.001). Eighty percent of the patients with serum levels <20 ng/ml (n = 9) had moderate-severe AD despite standard treatment. Vitamin D levels ≥20 ng/ml associated with baseline therapy strongly favored remission of atopic dermatitis (P = 0.03). No significant differences were found between patients with serum levels of ≥20 ng/ml vs. ≥30 ng/ml. CONCLUSIONS: Reaching serum levels of 25(OH)D > 20 ng/ml in conjunction with standard therapy is sufficient to achieve a reduction in severity (SCORAD) in patients with AD.

Primeras 2000 colecistectomías laparoscópicas ambulatorias en modalidad free-standing en un hospital público de la Argentina / Outcome of the first 2000 ambulatory, laparoscopic cholecystectomies with free-standing modality in a public hospital of Argentina

Antecedentes: la cirugía ambulatoria surge debido al aumento de la demanda y del gasto sanitario. Permite reducir el costo por procedimiento y la mayor eficacia se obtiene con la adopción de una unidad independiente pero que forma parte de un sistema de salud. Objetivo: Comunicar los primeros 2000 casos de colecistectomía laparoscópica ambulatoria en forma sistemática, en el primer hospital público independiente (free-standing) de la Argentina. Material y métodos: en 36 meses se realizaron las primeras 2000 colecistectomías laparoscópicas ambulatorias en régimen independiente (free-standing). Todos los casos fueron pacientes con patología no aguda, con IMC <35 kg/m², edad entre 13 y 65 años, categorizados ASA I o II. Resultados: se realizaron 1766 colecistectomías laparoscópicas convencionales y 234 colecistectomías mínimamente invasivas transumbilicales. Fueron trasladados a otras instituciones 12 pacientes, 3 de ellos por retardo en la recuperación y 9 por hallazgos intraoperatorios. Se diagnosticaron 3 litiasis coledocianas, 1 litiasis única y 2 múltiples durante la cirugía. Cuatro pacientes requirieron cirugía en otras instituciones por complicaciones asociadas con el procedimiento inicial. Conclusión: la colecistectomía laparoscópica en un hospital público free-standing es un proceso seguro, con tasas de complicaciones bajas si se usan los criterios de selección adecuados. La experiencia ganada con esta numerosa serie permitió afinar el sistema de selección y tratamiento.

Background: ambulatory surgery arose due to the increased demand and health expenses, allowing to reduce the cost per procedure. Efficiency may be maximized by adoption of an independent unit, but as part of a health system. Objective: to report the first 2000 cases of systematic, ambulatory laparoscopic cholecystectomies in the first public independent hospital (free-standing) of Argentina. Material and methods: in a free-standing institution, the first 2000 ambulatory laparoscopic cholecystectomies were performed in period of 36 months. All cases were non-acute, with BMI<35kg/m², aged between 13 and 65 years, categorized as ASA I or II. Results: conventional laparoscopic cholecystectomy was carried out in 1766 cases, while a minimally invasive transumbilical technique was done in 234. Twelve patients required transference to another institution, 3 of them due to delay in recovery and 9 due to intraoperative findings. Three cases of choledochalstones were diagnosed intraoperativelly (1 with a single stone and 2 with multiple). Four patients required surgery at a different institution in the immediate postoperative period due to complications associated with the initial surgery. Conclusions: laparoscopic cholecystectomy in an ambulatory free-standing public hospitalis safe, with low complication rates,if the appropriate selection criteria isused. The experience in this large series of cases allowed refining the selection and treatment criteria.

[Prevalencia y factores de riesgo para lesiones premalignas en pacientes menores de 55 años sometidos a colonoscopia en un hospital de tercer nivel]. / Prevalence and risk factors for premalignant lesions in patients younger than 55 years old founded on colonoscopy on a tertiary center.

ANTECEDENTES: El cáncer colorrectal es causa importante de mortalidad y la colonoscopia es efectiva para reducir su incidencia y mejorar la supervivencia con la resección de las lesiones precursoras. OBJETIVO: Determinar la prevalencia, las características y la histología de las lesiones en pacientes < 55 años en un hospital de tercer nivel. MÉTODO: Se realizó un estudio retrospectivo y observacional de enero de 2010 a diciembre de 2014 en el Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, con el reporte de 555 colonoscopias y los datos clínicos de las historias hospitalarias de los pacientes incluidos en el estudio. RESULTADOS: Los hallazgos fueron lesiones premalignas en el 40% de los pacientes, con pólipos en 98 casos y con un tamaño de 5.2 mm; de ellos, el 54% se localizaron en el colon, el 24% en el sigmoides, el 27% en el recto y el 1% en el ano. En los reportes se observó una prevalencia del 63% de pólipos neoplásicos (riesgo relativo [RR]: 2.3; intervalo de confianza del 95% [IC 95%]: 1.5-3.7) en pacientes con antecedente de tabaquismo, y del 42% (RR: 1.8; IC 95%: 1.2-2.6) con antecedente de consumo de alcohol. CONCLUSIONES: La prevalencia de lesiones premalignas es similar para los menores de 55 años. Esto indica la importancia del diagnóstico oportuno y de evitar la progresión. Sería conveniente extender el seguimiento a hospitales de segundo nivel en pacientes con factores de riesgo para ampliar lo reportado y contribuir a mejorar los resultados en la sanidad pública. BACKGROUND: Colorectal cancer is an important cause of mortality, colonoscopy is effective to reduce its incidence and improve survival with the resection of premalignant lesions. OBJECTIVE: To determine the prevalence, characteristics and histology of lesions in patients younger than 55 years of age in a tertiary hospital. METHOD: This is a retrospective observational study, we colected data at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, with the report of 555 colonoscopies, and clinical data from the hospital archives of medic histories of selected patients. RESULTS: Premalignant lesions were found on 40% of the patients. The findings were polyps in 98 cases with a size of 5.2 mm; 54% were located in the colon, 24% in the sigmoid, 27% in the rectum and 1% in the anus. A prevalence of 63% of neoplastic polyps was observed (RR: 2.3; 95% CI: 1.5-3.7) in smokers; and 42% (RR: 1.8; 95% CI: 1.2-2.6) in patients with alcohol consumption. CONCLUSIONS: The prevalence for premalignant lesions is similar for patients under 55 years of age. This highlights the importance of early diagnosis and avoiding progression. It would be convenient to extend the follow-up to second-level hospitals in patients with risk factors to contribute to improvement of public health system outcomes.