High-titer antichromatin antibody is associated with proliferative class IV of lupus nephritis

The antichromatin antibody (aCT) has been described as a useful marker for lupus nephropathy. The relevance of its nephritogenic potential may be appropriately evaluated in the context of renal histopathology. Therefore, the present study investigated the relationship of aCT with a particular histopathologic class of lupus nephritis (LN). Seventy-eight consecutive patients with systemic lupus erythematosus (ACR criteria) and active nephritis who underwent renal biopsy from 1999 to 2004 and with available frozen serum sample obtained at the time of biopsy were selected. aCT was measured by ELISA, and anti-dsDNA was measured by indirect immunofluorescence (IIF) and by ELISA. All renal biopsies were revised in a blinded manner by the same expert renal pathologist. Charts were extensively reviewed for demographic and renal features obtained at the time of biopsy. The prevalence of aCT (>= 20 U) was 59% with a mean titer of 74.3 +/- 38.7U. Both aCT-positive and aCT-negative groups of patients had similar age, gender distribution, duration of lupus, and duration of renal disease. Anti-dsDNA was detected by IIF in 29.5% and by ELISA in 42.3% of the patients. Concomitant presence of both antibodies was observed in 63% (29/46) [anti-dsDNA by ELISA] and 45.6% (21/46) [anti-dsDNA by IIF] of the patients. Lower serum levels of C3 (73% vs. 40%, P=0.0058) and C4 (82% vs. 46.7%, P=0.0021) were more commonly observed in aCT >= 20 U patients compared to the aCT-negative group. It is important to note that the use of a higher cut-off value (>= 40 U) for aCT test revealed a predominance of class IV LN (58% vs. 33%, P=0.039) in aCT >= 40 U compared to aCT<40 U group. The mean levels of proteinuria, serum albumin, and creatinine were markedly altered but were comparable in both groups (P >= 0.05). One fourth (26.3%) of the 19 patients with class IV LN and aCT >= 40 U had no detectable anti-dsDNA (ELISA). These data suggest that high-titer aCT seems to be a valuable biomarker for proliferative class IV of LN.

Male gender results in more severe lupus nephritis

Gender may produce different characteristics in the manifestation of systemic lupus erythematosus (SLE). The present study investigated the influence of gender on clinical, laboratory, autoantibodies and histopathological classes of lupus nephritis (LN). As much as 81 patients diagnosed with SLE (ACR criteria) and active nephritis, who underwent renal biopsy between 1999 and 2004, and who had frozen serum samples and clinical data available from the time of biopsy, were selected for this study. The presence of anti-P and antichromatin antibodies was measured using ELISA, and anti-dsDNA was measured using indirect immunofluorescence. All of the renal biopsies were reviewed in a blinded manner by the same expert renal pathologist. The charts were extensively reviewed for demographic and renal features obtained at the time of the biopsy. Of the 81 patients (13.6%), 11 were male SLE patients. Both male and female lupus patients were of similar age and race, and had similar durations of lupus and renal disease. The female patients had more cutaneous (95.7 vs. 45.5%, P = 0.0001) and haematological (52.9 vs. 18.2%, P = 0.04) involvements than the male SLE patients. In addition, the articular data, central nervous system analyses, serositis findings and SLEDAI scores were similar in both experimental groups. Positivity for anti-dsDNA, anti-ribosomal P and antichromatin did not differ between the two groups, and both groups showed similarly low C3 or C4 serum levels. Our analysis indicated that no histopathological class of LN was predominant in both males and females. Interestingly, the serum creatinine levels were higher in the male SLE patients compared to the female SLE group (3.16 +/- A 2.49 vs. 1.99 +/- A 1.54 mg/dL, P = 0.03), with an increased frequency of high creatinine (81.8 vs. 47.1%, P = 0.04) as well as renal activity index (7.6 +/- A 3.5 vs. 4.8 +/- A 3.5, P = 0.02). In addition, whilst the mean levels of proteinuria, cylindruria and serum albumin were markedly altered, they were comparable between both lupus men and women. Moreover, the frequencies of dialysis, renal transplantation and death were similar between the two groups. These data suggest that male patients had a more severe LN compared to women diagnosed with this renal abnormality.

Human leukocyte antigen-G expression after kidney transplantation is associated with a reduced incidence of rejection

HLA-G is a non-classic Human Leukocyte Antigen (HLA-G) Class I of low polymorphism and restricted tissue distribution that displays tolerogenic functions. In heart transplantation and in combined liver/renal allograft transplantation, the expression of HLA-G has been associated with a lower incidence of acute graft rejection episodes and absence of chronic dysfunction. Since the expression of HLA-G in renal biopsies has been investigated only in few patients who received a combined kidney and liver transplant, in this study we performed a cross-sectional study, systematically comparing the expression of HLA-G in post-transplanted renal grafts, stratifying patients according to the presence or absence of rejection. Patients and Methods: Seventy-three renal specimens (10 with acute rejection and 13 with chronic allograft nephropathy, and 50 with no signs of rejection) were immunohistochemically evaluated for HLA-G expression. Results: In the group as a whole, HLA-G molecules were detected in 40 cases (54.8%). Among specimens that presented HLA-G expression, 2 out of 40 (5%) exhibited acute rejection, 2 (5%) exhibited chronic allograft nephropathy, and the remaining 36 (90%) exhibited no signs of rejection. The comparison between patients with rejection and those without rejection showed that the expression of HLA-G was significantly increased in specimens exhibiting no signs of rejection (p<0.0001). Considering only patients with acute rejection, 8 out of 10 patients showed no HLA-G expression in their kidney biopsies when compared to patients exhibiting no signs of rejection and absence of HLA-G was observed in 14 out of 50 (p=0.0032). Similarly, considering only patients with chronic allograft nephropathy, absence of HLA-G expression was observed in I I out of 13 specimens, whereas in patients without rejection absence of HLA-G was observed in 14 out of 50 (p=0.003). Therapy with tacrolimus was significantly associated with the expression of HLA-G and a better graft prognosis. Conclusions: Our results suggest that HLA-G expression in the kidney allograft and the use of tacrolimus are associated with a lower frequency of acute renal rejection and chronic allograft nephropathy. (c) 2007 Elsevier B.V. All rights reserved.

Effects of high-intensity aerobic interval training vs. moderate exercise on hemodynamic, metabolic and neuro-humoral abnormalities of young normotensive women at high familial risk for hypertension

Exercise training has an important role in the prevention and treatment of hypertension, but its effects on the early metabolic and hemodynamic abnormalities observed in normotensive offspring of hypertensive parents (FH+) have not been studied. We compared high-intensity interval (aerobic interval training, AIT) and moderate-intensity continuous exercise training (CMT) with regard to hemodynamic, metabolic and hormonal variables in FH+ subjects. Forty-four healthy FH+ women (25.0+/-4.4 years) randomized to control (ConFH+) or to a three times per week equal-volume AIT (80-90% of VO(2MAX)) or CMT (50-60% of VO(2MAX)) regimen, and 15 healthy women with normotensive parents (ConFH-; 25.3+/-3.1 years) had their hemodynamic, metabolic and hormonal variables analyzed at baseline and after 16 weeks of follow-up. Ambulatorial blood pressure (ABP), glucose and cholesterol levels were similar among all groups, but the FH+ groups showed higher insulin, insulin sensitivity, carotid-femoral pulse wave velocity (PWV), norepinephrine and endothelin-1 (ET-1) levels and lower nitrite/ nitrate (NOx) levels than ConFH- subjects. AIT and CMT were equally effective in improving ABP (P<0.05), insulin and insulin sensitivity (P<0.001); however, AIT was superior in improving cardiorespiratory fitness (15 vs. 8%; P<0.05), PWV (P<0.01), and BP, norepinephrine, ET-1 and NOx response to exercise (P<0.05). Exercise intensity was an important factor in improving cardiorespiratory fitness and reversing hemodynamic, metabolic and hormonal alterations involved in the pathophysiology of hypertension. These findings may have important implications for the exercise training programs used for the prevention of inherited hypertensive disorder. Hypertension Research (2010) 33, 836-843; doi:10.1038/hr.2010.72; published online 7 May 2010

Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension

Exercise is an effective intervention for treating hypertension and arterial stiffness, but little is known about which exercise modality is the most effective in reducing arterial stiffness and blood pressure in hypertensive subjects. Our purpose was to evaluate the effect of continuous vs. interval exercise training on arterial stiffness and blood pressure in hypertensive patients. Sixty-five patients with hypertension were randomized to 16 weeks of continuous exercise training (n=26), interval training (n=26) or a sedentary routine (n=13). The training was conducted in two 40-min sessions a week. Assessment of arterial stiffness by carotid-femoral pulse wave velocity (PWV) measurement and 24-h ambulatory blood pressure monitoring (ABPM) were performed before and after the 16 weeks of training. At the end of the study, ABPM blood pressure had declined significantly only in the subjects with higher basal values and was independent of training modality. PWV had declined significantly only after interval training from 9.44 +/- 0.91 to 8.90 +/- 0.96 m s(-1), P=0.009 (continuous from 10.15 +/- 1.66 to 9.98 +/- 1.81 m s(-1), P-ns; control from 10.23 +/- 1.82 to 10.53 +/- 1.97 m s(-1), P-ns). Continuous and interval exercise training were beneficial for blood pressure control, but only interval training reduced arterial stiffness in treated hypertensive subjects. Hypertension Research (2010) 33, 627-632; doi:10.1038/hr.2010.42; published online 9 April 2010

Physical activity profile in heart failure patients from a Brazilian tertiary cardiology hospital

Background: Physical activity (PA) has proven benefits in the primary prevention of heart diseases such as heart failure (HF). Although it is well known, HF PA habits and physicians` advice have been poorly described. The aim of this study was to investigate if physicians were advising HF patients to exercise and to quantify patients` exercise profiles in a complex cardiology hospital. Methods: All 131 HF patients (80 male, average age 53 +/- 10 years, NYHA class I-V, left ventricular ejection fraction 35 +/- 11%, 35 ischemic, 35 idiopatic , 32 hypertensive and 29 with Chagas disease) went to the hospital for a HF routine check-up. On this occasion, after seeing the physician, we asked the patients if the physician had advised them about PA. Then, we asked them to fill in the international physical activity questionnaire (IPQA) Short Form to classify their PA level. Results: Our data showed a significant difference between patients who had received any kind of PA advice from physicians (36%) and those who had not (64%, p<0.0001). Using the IPAQ criteria, of the 36% of patients who had received advice, 12.4% were classified as low and 23.6% as moderate. Of the 64% of patients who did not receive advice, 26.8% were classified as lowand 37.2% as moderate. Etiology (except Chagas), functional class, ejection fraction, sex and age did not influence the PA profile. Conclusions: Physicians at a tertiary cardiology hospital were not giving patients satisfactory advice as to PA. Our data supports the need to strengthen exercise encouragement by physicians and for complementary studies on this area. (Cardiol J 2010; 17, 2: 143-148)

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

Background: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity. Methods: Male OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping. Results: We studied 266 males with OSA (age = 48 +/- 13y, body mass index = 29 5kg/m(2), AHI = 34 +/- 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast. the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and 11 genotype (OR = 0.27). Conclusions: Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA. (C) 2009 Elsevier B.V. All rights reserved.

Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR

Aneas I, Rodrigues MV, Pauletti BA, Silva GJ, Carmona R, Cardoso L, Kwitek AE, Jacob HJ, Soler JM, Krieger JE. Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR. Physiol Genomics 37: 52-57, 2009. First published January 6, 2009; doi: 10.1152/physiolgenomics.90299.2008. - To dissect the genetic architecture controlling blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four previously mapped BP quantitative trait loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway rat (BN) averaging 13 - 29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12 or 13 generations. Under normal salt intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect. On high salt intake (1% NaCl in drinking water for 2 wk), the chromosome 16 QTL had a marked impact on SBP, as did the QTLs on chromosome 2a and 2c (18, 17, and 19 mmHg, respectively), but not the QTL on chromosome 4. Thus these four QTLs affected BP phenotypes differently: 1) in the presence of high salt intake (chromosome 16), 2) only associated with normal salt intake (chromosome 4), and 3) regardless of salt intake (chromosome 2c and 2a). Moreover, salt sensitivity was abrogated in congenics SHR. BN2a and SHR. BN16. Finally, we provide evidence for the influence of genetic background on the expression of the mapped QTLs individually or as a group. Collectively, these data reveal previously unsuspected nuances of the physiological roles of each of the four mapped BP QTLs in the SHR under basal and/or salt loading conditions unforeseen by the analysis of the F2 cross.

Vitamin D intoxication: a cause of hypocalcaemia and acute renal failure in a HIV patient

Hypercalcaemia in patients with HIV infection is usually associated with specific conditions such as lymphoma and granulomatous diseases. We described a case of severe hypercalcaemia consequent to vitamin D intoxication and secondary renal failure in a HIV patient under tenofovir using. Serum creatinine and calcium returned to near normal levels after vitamin D discontinuation, saline and furosemide administration. Some aspects of the drug-induced nephropathy are discussed.

Effects of bilateral adrenalectomy on systemic kainate-induced activation of the nucleus of the solitary tract. Regulation of blood pressure and local neurotransmitters

Glutamatergic transmission through metabotropic and ionotropic receptors, including kainate receptors, plays an important role in the nucleus of the solitary tract (NTS) functions. Glutamate system may interact with several other neurotransmitter systems which might also be influenced by steroid hormones. In the present study we analyzed the ability of systemic kainate to stimulate rat NTS neurons, which was evaluated by c-Fos as a marker of neuronal activation, and also to change the levels of NTS neurotransmitters such as GABA, NPY, CGRP, GAL, NT and NO by means of quantitative immunohistichemistry combined with image analysis. The analysis was also performed in adrenalectomized and kainate stimulated rats in order to evaluate a possible role of adrenal hormones on NTS neurotransmission. Male Wistar rats (3 month-old) were used in the present study. A group of 15 rats was submitted either to bilateral adrenalectomy or sham operation. Forty-eight hours after the surgeries, adrenalectomized rats received a single intraperitoneal injection of kainate (12 mg/kg) and the sham-operated rats were injected either with saline or kainate and sacrificed 8 hours later. The same experimental design was applied in a group of rats in order to register the arterial blood pressure. Systemic kainate decreased the basal values of mean arterial blood pressure (35%) and heart rate (22%) of sham-operated rats, reduction that were maintained in adrenalectomized rats. Kainate triggered a marked elevation of c-Fos positive neurons in the NTS which was 54% counteracted by adrenalectomy. The kainate activated NTS showed changes in the immunoreactive levels of GABA (143% of elevation) and NPY (36% of decrease), which were not modified by previous ablation of adrenal glands. Modulation in the levels of CGRP, GAL and NT immunoreactivities were only observed after kainate in the adrenalectomized rats. Treatments did not alter NOS labeling. It is possible that modulatory function among neurotransmitter systems in the NTS might be influenced by steroid hormones and the implications for central regulation of blood pressure or other visceral regulatory mechanisms control should be further investigated.

Resistance Exercise Intensity Progression in Older Men

Our purpose was to examine possible influences of age on resistance exercise (RE) intensity progression in men. Twenty-four men, divided in young sedentary (YS; n = 10; 25.9 +/- 3.7 years), older sedentary (OS; n = 7; 67.4 +/- 5.2 years), and older runners (OR; n = 7; 71.3 +/- 3.0 years), underwent a 2 times-a-week RE program for 13 weeks. Muscle strength was assessed before and after training by 1-repetition maximum test. RE workloads were recorded for each exercise session, and increases of 5-10% were made whenever adaptation occurred. Muscle strength improved similarly in all groups after RE (P < 0.001). Relative RE intensity progression was not significantly different between YS and OS, except for a greater increase in calf raise relative workload observed in YS (P < 0.05). In contrast, OR displayed greater relative workload increase in 7 and 6 exercises than YS and OS, respectively (P < 0.05). The RE was safe as no injuries or major muscle pain were observed in either group. These results suggest that healthy sedentary older men are capable to exercise and increase RE intensity in the same way as young men, while physically active older men are capable to increase RE intensity in greater way than sedentary young and older men.

Mucosal leishmaniasis: description of case management approaches and analysis of risk factors for treatment failure in a cohort of 140 patients in Brazil

Background Mucosal leishmaniasis is caused mainly by Leishmania braziliensis and it occurs months or years after cutaneous lesions. This progressive disease destroys cartilages and osseous structures from face, pharynx and larynx. Objective and methods The aim of this study was to analyse the significance of clinical and epidemiological findings, diagnosis and treatment with the outcome and recurrence of mucosal leishmaniasis through binary logistic regression model from 140 patients with mucosal leishmaniasis from a Brazilian centre. Results The median age of patients was 57.5 and systemic arterial hypertension was the most prevalent secondary disease found in patients with mucosal leishmaniasis (43%). Diabetes, chronic nephropathy and viral hepatitis, allergy and coagulopathy were found in less than 10% of patients. Human immunodeficiency virus (HIV) infection was found in 7 of 140 patients (5%). Rhinorrhea (47%) and epistaxis (75%) were the most common symptoms. N-methyl-glucamine showed a cure rate of 91% and recurrence of 22%. Pentamidine showed a similar rate of cure (91%) and recurrence (25%). Fifteen patients received itraconazole with a cure rate of 73% and recurrence of 18%. Amphotericin B was the drug used in 30 patients with 82% of response with a recurrence rate of 7%. The binary logistic regression analysis demonstrated that systemic arterial hypertension and HIV infection were associated with failure of the treatment (P < 0.05). Conclusion The current first-line mucosal leishmaniasis therapy shows an adequate cure but later recurrence. HIV infection and systemic arterial hypertension should be investigated before start the treatment of mucosal leishmaniasis. Conflicts of interest The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

Posterior reversible encephalopathy syndrome after liver transplantation in children: A rare complication related to calcineurin inhibitor effects

PRES is a neuroclinical and radiological syndrome that results from treatment with calcineurin inhibitor immunosuppressives. Severe hypertension is commonly present, but some patients may be normotensive. We report herein two children who received liver transplants, as treatment for biliary atresia in the first case and for Alagille`s syndrome in the second one. In the early postoperative, both patients presented hypertension and seizures. In both cases, the image findings suggested the diagnosis of PRES. The CT scan showed alterations in the posterior area of the brain, and brain MRI demonstrated parietal and occipital areas of high signal intensity. Both children were treated by switching the immunosuppressive regimen and controlling arterial blood pressure. They displayed full recuperation without any neurologic sequelae. Probably, the pathophysiology of PRES results from sparse sympathetic innervation of the vertebrobasilar circulation, which is responsible for supplying blood to the posterior areas of the brain. In conclusion, all liver-transplanted children who present with neurological symptoms PRES should be considered in the differential diagnosis, although this is a rare complication. As treatment, we recommend rigorous control of arterial blood pressure and switching the immunosuppressive regimen.

Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR

Crajoinas RO, Lessa LMA, Carraro-Lacroix LR, Davel APC, Pacheco BPM, Rossoni LV, Malnic G, Girardi ACC. Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR. Am J Physiol Renal Physiol 299:F872-F881, 2010. First published July 14, 2010; doi:10.1152/ajprenal.00654.2009.-Abnormalities in renal proximal tubular (PT) sodium transport play an important role in the pathophysiology of essential hypertension. The Na(+)/H(+) exchanger isoform 3 (NHE3) represents the major route for sodium entry across the apical membrane of renal PT cells. We therefore aimed to assess in vivo NHE3 transport activity and to define the molecular mechanisms underlying NHE3 regulation before and after development of hypertension in the spontaneously hypertensive rat (SHR). NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT from young prehypertensive SHR (Y-SHR; 5-wk-old), adult SHR (A-SHR; 14-wk-old), and age-matched Wistar Kyoto (WKY) rats. We found that NHE3-mediated PT bicarbonate reabsorption was reduced with age in the SHR (1.08 +/- 0.10 vs. 0.41 +/- 0.04 nmol/cm(2)xs), while it was increased in the transition from youth to adulthood in the WKY rat (0.59 +/- 0.05 vs. 1.26 +/- 0.11 nmol/cm(2)xs). Higher NHE3 activity in the Y-SHR compared with A-SHR was associated with a predominant microvilli confinement and a lower ratio of phosphorylated NHE3 at serine-552 to total NHE3 (P-NHE3/total). After development of hypertension, P-NHE3/total increased and NHE3 was retracted out of the microvillar microdomain along with the regulator dipeptidyl peptidase IV (DPPIV). Collectively, our data suggest that the PT is playing a role in adapting to the hypertension in the SHR. The molecular mechanisms of this adaptation possibly include an increase of P-NHE3/total and a redistribution of the NHE3-DPPIV complex from the body to the base of the PT microvilli, both predicted to decrease sodium reabsorption.

Flow-through peritoneal dialysis in neonatal enema-induced hyperphosphatemia

Fleet enemas are hypertonic solutions with an osmotic action and a high concentration of phosphate. When retained in the human body they have a great toxic potential, causing severe hydro-electrolyte disorders in children, especially in newborns. We report the case of a previously healthy 8-day-old newborn who needed neonatal intensive care treatment after the inadvertent administration of an osmotically active hypertonic phosphate enema. Taking into account that phosphate removal by peritoneal dialysis (PD) strongly depends on total dialysate turnover, we chose continuous flow PD (CFPD) as the treatment option, with a successful outcome. Clinical experience with this dialytic modality is limited to a few case reports in pediatric and adult patients. To the best of our knowledge, we report here the first description of CFPD in the setting of acute phosphate nephropathy in the neonatal period. The modality of PD described here has potential as an alternative management option as it is a highly efficient, methodologically simple, and low-cost method without any need for sophisticated equipment. Physicians and parents should be aware of the adverse effects of a hypertonic phosphate enema and should never use these medications in infants and newborns.