Graph of % of drug release versus time was plotted as follows. In initial 5 h 20% of drug release

has occurred. In initial 1 h 10% drug release was obtained. Once addition of pancreatin was done, drug release increased slightly. After 5 h 20% of drug release was occurred. But once addition of rat cecal content is carried out drug release increased rapidly. In next 2 h 97% of drug was released. Results were shown in Fig. 1. This indicates that after crosslinking of chitosan, it retains its specific biodegradability by colonic micro-organisms.19 Scanning electron microscopy was carried out to find out morphology of microparticles. Results this website of SEM are as shown in Fig. 2. SEM images indicate morphology of microparticles which was smooth in appearance and spherical in shape JQ1 solubility dmso and having size less than 5 μm. Small size may be contributed to the microparticles due to apparatuses size of atomizer high atomization pressure during spray drying. Surface of the microparticles is smooth

without any grooves which indicate that coating has occurred uniformly. DSC of the microparticles was carried out to check possible interaction in between drug and polymer. DSC graph showed endothermic peak near 160 °C which is indication of presence of drug. In DSC graph of pure budesonide endothermic peak was also observed at 160 °C as shown in Fig. 4. FTIR spectra of microparticles was recorded by using Bruker alpha. Microparticles showed the presence of particular groups which are present in FTIR spectra of budesonide as shown in Fig. 3. Particle size analysis was performed on Malvern Mastersizer.

Maximum particle size was found be distributed in the range of 2–5 μm. Results were shown in Fig. 5. Less particle size is obtained which may be contributed to the method of microsphere preparation which is spray drying. Other methods such as solvent evaporation, emulsion method generates particles of higher size. All authors have none to declare. “
“Tuberculosis (TB) is one of the leading causes of death due to the single infectious organism in the world. Approximately two billion PD184352 (CI-1040) people have been infected with causative organism Mycobacterium tuberculosis (MTB) Every 20 s someone dies of TB. 1 The increase of TB during recent years was largely due to HIV-1 infection immigration increased trade and globalization. 2 and 3 Furthermore numerous studies have shown that TB is a cofactor in the progression of HIV infection. Mycobacterium tuberculosis (MTB) remains a major health problem affecting one third of the world population and prevailing as the leading infectious cause of death. About 32% of the world’s population (1.9 billions people) is affected with TB. 4 and 5 The current global AIDS epidemic has increased the incidence of tuberculosis (TB) in both the developing and developed world. So there is urgency for prompt diagnosis of MTB infection causing TB.

The trained NVHL rats were significantly better than the exposed NVHL rats in sessions 2–4, indicating that adolescent training promoted adult cognition. We then compared the trained NVHL and the trained control rats to assess whether adolescent cognitive training was normalizing. The two groups did not differ (Figure 2C), suggesting that adolescent cognitive training improved cognitive control to normal. We verified that the improved cognitive performance of NVHL rats in the T-maze was due to adolescent training by retesting

all the rats on the CP-868596 in vitro two-frame place avoidance task (Figure 2D). The NVHL rats that were trained as adolescents were not impaired, but the NVHL rats that were only exposed to the rotating arena as adolescents were consistently impaired in avoiding both the original shock zone (Figure 2D, left) and the reversed shock zone in the conflict avoidance test (Figure 2D, right). Only the exposed NVHL rats were significantly impaired, compared to the other groups, in both the original and reversed shock zones (p values < 0.05). We conclude that adolescent cognitive training has adult procognitive effects that include preventing cognitive control deficits following a neonatal lesion and that this benefit can generalize to other tests of cognition. Physical changes in

the degree of the adult hippocampal lesion could not account for the cognitive benefits of adolescent training because there was no correspondence between lesion extent and cognitive performance (Figure 3). Although the adolescent-trained and adolescent-exposed MRIP NVHL rats show similar degree of lesion of septal, intermediate, and temporal hippocampus, cognitive performance Ibrutinib manufacturer was markedly different. We then tested whether early cognitive training caused functional changes, focusing on neural synchrony, which may be disturbed in patients with schizophrenia (Gandal et al., 2012; Moran and Hong, 2011; Uhlhaas and Singer, 2010). Local field potentials (LFPs) in hippocampus and the medial prefrontal cortex (mPFC) of adult control rats

were compared from recordings during home cage behaviors and during the two-frame task to first identify changes that were related to cognitive performance. Neural synchrony between two electrode locations was measured as the frequency-specific phase locking value (Figure S2). In sham control rats, compared to being in the home cage, performing the task produced a robust increase of interhippocampus phase synchrony across delta, theta, and beta frequencies but not gamma (Figure 4A). These changes were specific to hippocampus because no such differences were found in either inter-mPFC or inter-hippocampus-mPFC synchrony (Figure S3). Because interhippocampus synchrony was related to two-frame performance but synchrony involving the mPFC was not, we focused on hippocampal synchrony in further analyses. We then compared interhippocampal synchrony of adult control and NVHL rats while they were performing the two-frame task.

21, 95% CI 0.05 to 0.85), reduced the duration of ventilatory assistance (MD –2.0 days, 95% CI –1.5 to –2.6) and reduced overall hospital length of stay (MD –0.75 days, 95% CI –0.1 to –1.4).43 These results were heavily influenced by trials using positive pressure techniques, which generally had more favourable outcomes than those that did not use positive pressure. In addition to the Cochrane review,44 there are two large trials of airway clearance techniques for AECOPD that have implications Luminespib manufacturer for practice. A randomised controlled equivalence trial in 526 people hospitalised

with an AECOPD found no difference in quality of life at 6 months between those who received manual chest physiotherapy (active cycle of breathing technique including FET, percussion and vibration) and those who received only advice about positioning and active cycle of breathing technique.44 There was no difference in hospital length of stay between groups. The trial had broad inclusion criteria and participants did not have to be productive of sputum to take part. The

results of this study provide confidence that manual chest physiotherapy techniques do not have a routine role for people with AECOPD. Another randomised trial comparing positive expiratory pressure therapy (PEP) and FET to usual physiotherapy care in 90 people hospitalised with AECOPD found no difference between groups in the primary outcome – the Breathlessness,

Cough and Sputum Scale – at any time point during the 6-month followup.45 Although dyspnoea improved more rapidly in the PEP group in the first 8 CP-673451 solubility dmso weeks, by 6 months there were no clinically relevant or statistically significant differences between groups. When this trial is combined with previous airway clearance technique studies in a meta-analysis, the body of evidence no longer suggests an overall benefit of the techniques during AECOPD in the need for ventilatory assistance (Figure 2; for a more detailed forest plot, see Figure 3 on the eAddenda).45, 46, 47, 48 and 49 The differing results between this trial and previous studies may be related to the population studied, which included fewer people who needed ventilatory assistance, or to the more active comparison group, where usual physiotherapy care included early mobilisation.49 In summary, current evidence below for the effects of airway clearance techniques in AECOPD is inconsistent across trials, but does not suggest an overall benefit of airway clearance techniques for hospitalised patients. Whilst positive outcomes have been reported in the sickest patients (ie, those requiring or at risk of requiring invasive or non-invasive ventilatory assistance) in the most recent Cochrane review,43 these effects are small and are not supported by the results of a recent large trial.49 There is no evidence that manual chest physiotherapy techniques are useful in AECOPD.

The temporal distribution, with each serotype predominating alternatively during each season, may also be seen as the cyclical nature of rotavirus infections [26]. However, the study period was not long enough to confirm these yearly or cyclical changes. In conclusion, this cohort study demonstrates selleck the importance of rotavirus as a cause of disease in young children in India, and its contribution to severe disease. Rotavirus infection in the neonatal period

in the community is rarely reported, and the influence of such infections on subsequent vaccination with rotavirus vaccines needs to be elucidated. The roles of early infections, and high rates of re-infections outside of a rotavirus season, specific genotypes in infection and disease in different regions of the world also need further investigation to better understand virus circulation, transmission and pathogenicity. None declared. “
“Rotavirus is the most severe cause of diarrheal illness among infants and young children. Worldwide, nearly 453,000 children less than 5 years of age die each

year due to rotavirus infection of which about 98,621 die in India each year [1]. TSA HDAC Besides high mortality, rotavirus infection annually results in an estimated 457,000–884,000 hospitalizations and 2 million outpatient visits in children less than 5 years of Oxalosuccinic acid age [2]. India spends approximately 41–72 million USD each year in

medical costs treating rotavirus related diarrhea [2]. High rotavirus incidence, economic burden and loss of human life emphasize the need for inclusion of the rotavirus vaccine in the national immunization program. Two rotavirus vaccines, Rotateq® and Rotarix® have been licensed in several countries worldwide and are available in India. Although they have been highly successful in reducing rotavirus related hospital admissions in developed countries, their efficacy has been rather low in developing countries [3]. An indigenous Indian neonatal vaccine, ROTAVAC successfully completed the Phase III clinical trials and is expected to be licensed in India in early 2014. Once licensed, ROTAVAC would be a better alternative for inclusion in the national vaccination program and would also be beneficial for other developing countries due to low vaccine cost and large target population for vaccination. Rotavirus vaccine efficacy depends largely on the 2 major outer viral proteins, VP7 (glycoprotein) and VP4 (protease sensitive protein) which are the prime targets for neutralizing antibodies and have been shown to generate protective immunity. They also form the basis of RV genotyping in which the VP7 protein defines the G-types and the VP4 defines the P-types [4]. At least, 27 G and 35 P genotypes have been identified in humans and animals [5].

The two groups were comparable with respect to gender and age (Table 2). Of the 301 infants, 297 subjects received at least 1 vaccine/placebo dose, and participated in the intensive safety surveillance. Over the course of 42 days, 14 (9.5%) participants receiving rotavirus vaccine experienced a SAE compared with 23 (15.3%) among

those receiving the placebo, (p = 0.13) ( Table 3). The Selleck Venetoclax most common serious adverse events for participants receiving rotavirus vaccine were pneumonia (7.5%) and gastroenteritis (6.8%). The most common serious adverse events for participants in the placebo group were gastroenteritis (11.3%), malaria (5.3%), and pneumonia (5.3%). Four deaths on or before day 42 after any vaccination [1 (0.7%) in the vaccine group due to HIV/pneumonia and 3 (2.0%) in the placebo group due to therapeutic toxicity, febrile infection and unknown cause] were reported. None of these deaths were considered by the investigators to be vaccine-related. Clinicians (blinded as to vaccine or placebo status) indicated that they thought SAEs in 3 (2%) vaccine recipients and in 9 (6%) placebo recipients in the intensive safety surveillance cohort were related to receiving the study MS-275 supplier vaccine. These 12 SAEs were due to gastroenteritis. There were no statistical differences for overall or cause-specific SAEs by treatment group. Serious and non-serious adverse events were experienced among

137/147 (93.2%) vaccine recipients and 147/150 (98.0%) placebo recipients respectively (RR = 0.95, 95% CI 0.91–1.00; p = 0.05) ( Table 4). The most common clinical adverse events for participants in the vaccine group were pyrexia (65.3%), cough (59.9%), and diarrhea (48.3%). Likewise, the most common clinical adverse events for the placebo group were pyrexia (64.7%), cough (59.3%), and diarrhea (42.7%). There were no statistically significant differences between the two groups with

respect to vomiting, diarrhea and elevated temperature. Among enrolled participants, 1167 (89.8%) consented to HIV testing and 1158 (88.5%) were tested. Of the 1158, 21/581 (3.6%) children in the vaccine group and 17/577 (2.9%) in the placebo group were found to be HIV-infected at enrolment. Among these, the median CD4% others at enrollment for the vaccine recipients (n = 14 with CD4%) was 26% (range: 13–54%) and for placebo recipients (n = 12 with CD4%) was 21% (range: 9–35%) (p = 0.17). 37/38 (97.4%) HIV-infected participants completed SAE surveillance or were in the intensive safety cohort (21/649 vaccine recipients and 16/643 placebo recipients). Five of 21 (23.8%) vaccine recipients and 2/16 (12.5%) placebo recipients with safety follow up experienced an SAE within 14 days of any dose (p = 0.67) ( Table 5A); the most common SAE for both HIV-infected treatment groups was reported as HIV infection (19% in the vaccine group and 6.3% in the placebo group (p = 0.36) ( Table 5B). One of 21 (4.8%) vaccine recipients and 1/16 (6.

3 μCi/mmol) and [3H]DA ([3H]dihydroxyphenylethylamine, [3H]dopamine; 46 μCi/mmol) were purchased from PerkinElmer, Boston, MA. [3H]1-Methyl-4-phenylpyridinium

([3H]MPP+; 85 μCi/mmol) was supplied by American Radiolabeled Chemicals (St. Louis, MO). Ipatasertib in vivo Paroxetine was from Santa Cruz Biotechnology, mazindole, serotonin, levamisole, cocaine, aminorex, nisoxetine, D-amphetamine, and monensin were purchased from Sigma–Aldrich Co. The samples used in this study were obtained from drug users participating voluntarily and anonymously in the ‘checkit!’ drug prevention program. Three to ten milligrams of substance were scraped into a tapered 2 ml test vial and weighed with an analytical balance. The substance was dissolved in 1 mL of methanol and vortex mixed for 1 min. The solution was centrifuged for 3 min at 10,000g in an Eppendorf centrifuge. Ten microliters of the supernatant were diluted with 0.4 mL of internal standard solution (trazodone 50 μg/mL dissolved in 10 mM aqueous ammonium formate buffer), 2 μl of the solution was analysed

with reversed phase HPLC and LC/mass spectrometry coupling as described in a previous study ( Rosenauer et Bioactive Compound Library al. 2013). The generation of HEK293 cell lines expressing the human isoforms of SERT, NET, or DAT (HEK-SERT, HEK-DAT, or HEK-NET, respectively) was described earlier (Scholze et al., 2002). HEK293 cells stably expressing either neurotransmitter transporter were seeded onto poly-d-lysine-coated 96-well

plates (40,000 cells/well), 24 h prior to the experiment. For inhibition experiments, the specific activity of the tritiated substrate was kept constant: [3H]DA, 0.1 μM; [3H]MPP+, 0.015 μM; [3H]5-HT, 0.1 μM. Assay conditions were used as outlined earlier ( Sucic et al., 2010). In brief, the cells were washed twice with Krebs–Ringer–HEPES buffer (KHB; composition: 25 mM HEPES·NaOH, pH 7.4, 120 mM NaCl, 5 mM KCl, 1.2 mM CaCl2, and 1.2 mM Edoxaban MgSO4 supplemented with 5 mM d-glucose). Then, the diluted reference and sample compounds were added and incubated for 5 min to allow for equilibration with the transporters. Subsequently, the tritiated substrates were added and the reaction was stopped after 1 min (SERT and DAT) and 3 min (NET), respectively. Cells were lysed with 1% SDS and the released radioactivity was quantified by liquid scintillation counting. All determinations were performed in duplicate or triplicate. For release studies, HEK-SERT, HEK-NET, or HEK-DAT cells were grown overnight on round glass coverslips (5-mm diameter, 40,000 cells per coverslip) placed in a 96-well plate and preloaded with 0.4 μM [3H]dopamine, 0.1 μM [3H]MPP+, or 0.4 μM [3H]5-HT for 20 min at 37 °C in a final volume of 0.1 mL/well. Coverslips were then transferred to small superfusion chambers (0.2 ml) and superfused with KHB (25 °C, 0.7 ml × min−1) as described (Scholze et al., 2002).

Tout comme l’obésité, les prévalences du SMet et du DT2 s’élèvent avec l’âge. Et fait de nombreuses fois démontré par les études épidémiologiques, elles restent

supérieures chez l’homme à ce qui est observé dans le sexe féminin. A découlé fort logiquement Antidiabetic Compound Library datasheet de ce constat, la question du rôle éventuel des stéroïdes sexuels dans cette différence liée au genre. De nombreuses études ont mis en évidence, chez l’homme adulte, un lien indiscutable entre abaissement du taux de testostérone plasmatique et syndrome d’insulino-résistance. Insulino-résistance et hypotestostéronémie sont par ailleurs impliqués dans la physiopathologie de plusieurs facteurs de risque vasculaire : hypertension artérielle, trouble de l’équilibre glycémique, dyslipidémie [1], [2], [3] and [4]. Deux constations supplémentaires ont amené à évaluer plus précisément l’équilibre androgénique des hommes suivis pour obésité, SMet ou DT2 : • la fréquence de ces anomalies métaboliques s’élève avec l’âge tandis que parallèlement la sécrétion testiculaire endocrine décline ; Chez l’homme, une baisse de la testostéronémie a été démontrée dans chacun des IWR-1 datasheet trois cadres pathologiques que constituent obésité, SMet et DT2. Il s’agit donc bien

là d’un point commun supplémentaire à ces trois entités, point commun dont l’identification a amené à s’interroger sur son implication physiopathologique, sa valeur pronostique et l’intérêt thérapeutique d’un rééquilibrage du statut androgénique. Une réduction du taux de testostérone plasmatique, dont l’ampleur est inversement corrélée à l’index de masse corporelle (IMC), a été mise en évidence chez l’homme adulte en surcharge pondérale. Dans le surpoids simple ou l’obésité non morbide, le taux de testostérone libre reste not situé dans les limites de la normale pour la tranche d’âge considérée. Dans ces deux situations, l’abaissement de la testostérone totale est en effet liée à la diminution du taux de la Sex Hormone-Binding Globulin (SHBG), protéine porteuse des stéroïdes sexuels encore dénommée Testosterone-estradiol-Binding Globulin (TeBG) dont le taux est négativement corrélé

à l’IMC ( figure 1) [5]. L’obésité massive s’accompagne, par contre, d’une réduction de l’ensemble des fractions, libre et liée, de la testostérone plasmatique [6]. L’obésité androïde s’associe à une insulino-résistance. Testostéronémie totale et taux de SHBG plasmatique en représenteraient des marqueurs, susceptibles également d’être impliqués dans son développement et, à un stade évolutif ultérieur, à celui d’un DT2. Il a été montré que le taux de testostérone plasmatique était fréquemment plus bas dans la population d’hommes atteints d’insulino-résistance que dans une population du même âge indemne de pathologie quelconque [2], [7] and [8]. Les résultats de ces études font même l’hypothèse qu’un taux bas de testostérone plasmatique exposerait à un risque plus élevé de développement d’un DT2.

, 2007), one medium quality

(Trief et al., 1995) and three low quality studies (Follick et al., 1985 and Klapow et al., 1995 and Masters et al., 2007), report on the association of informal social support with psychological factors (e.g. depression, kinesiophobia, catastrophising). Four studies, one high quality (Feleus et al.), one medium (Trief et al.) and two low quality (Klapow et al., Masters et al.) all stratified groups of spinal pain patients dependent on psychological outcomes, and all report significant group differences, with those more severely affected by psychological outcome having lower levels of satisfaction with social CP-690550 manufacturer support. Best evidence synthesis indicates moderate evidence of an association between satisfaction with social support and psychological outcomes in patients with nonspecific spinal pain. Frequency of interaction with social support and psychological outcome is reported by one low quality study (Follick et al.). The study reports that social interaction correlates with psychological scales Cytoskeletal Signaling inhibitor of the Minnesota Multiphasic Personality Inventory (MMPI). Best evidence synthesis indicates inconclusive evidence on the association between frequency of interaction and psychological outcomes. No studies

reported associations with emotional, instrumental or informational support, appraisal or network size. Five cohort studies, three of high quality (Khatun et al., 2004, Muramatsu et al., 1997 and Power et al., 2001)

and two of medium quality (Larsen and Leboeuf-Yde, 2006 and Linton, 2005), considered informal social support and the occurrence of spinal pain (see Table S4). Three high quality studies (Khatun et al., Muramatsu et al., Power et al.) report the association between emotional social support and occurrence Cediranib (AZD2171) of spinal pain. Khatun et al. reports of a small association for females with neck pain, Power et al. reports no effect for back pain and Muramatsu et al. report a small inverse effect with emotional support increasing risk of back pain. Best evidence synthesis indicates inconclusive evidence of an effect of emotional support on risk of spinal pain. Two high quality studies (Muramatsu et al., Power et al.) report on the effects of instrumental support. Muramatsu et al. report on a slight decrease (2%) in risk of low back pain with higher instrumental support, and Power et al. report no significant effect. Best evidence synthesis indicates inconsistent findings for the effect of instrumental support on spinal pain. Two studies, one high quality (Khatun et al.) and one medium quality (Larsen and Leboeuf-Yde) report the effects of social network size from friends and family and risk of spinal pain. Both studies report no significant associations, indicating inconclusive evidence using best evidence synthesis. One medium quality study (Linton et al.

Flow cytometric analysis of the interaction of the generated antibodies with diverse pneumococci showed that antibodies to PspA 245/00 and 94/01 were able to increase complement deposition on the widest range of pneumococci tested. The complement deposition on the different pneumococci appeared to be also influenced by the serotype. We observed that some serotypes exhibited an increased complement deposition in the absence of anti-PspA antibodies, as demonstrated previously with serotype 6B strains [31]. We tested the ability of these antisera to induce the complement deposition in pneumococcal

strains bearing family 2 PspAs (data not shown), and no increase in complement deposition was observed. This result is in accordance with our previous

findings Perifosine price [21], and suggests that, although some family 1 molecules can broaden cross-reactivity within this family, this effect is not extended to family 2. Our results demonstrated a significant variability in the cross-reactivity XAV-939 molecular weight of antisera generated against PspAs of the same clade, which correlates with differences in antibody mediated complement deposition on pneumococci. In order to correlate the results of cross-reactivity with protection, we evaluated the ability of the two most cross-reacting sera to promote the opsonophagocytosis of different pneumococcal strains by peritoneal phagocytes. Since it has been difficult to show killing using the classical OPA by anti-PspA antisera (unpublished data), we have optimized this assay in order to overcome the protective effect of the capsule. Using peritoneal cells over recovered from mice stimulated with a polyclonal T-cell activator, we were able to demonstrate the ability of anti-PspA antibodies to induce complement mediated phagocytosis of pneumococci of different serotypes.

The results demonstrate that both sera were able to induce complement-mediated phagocytosis leading to a minimum reduction of 30% on the number of pneumococci. This effect was observed for pneumococci of diverse capsular types, including serotypes 1, 3 and 6B, demonstrating the viability of this adapted opsonophagocytic assay for measuring the protective role of anti-PspA antibodies, which can overcome the inhibitory effects of different capsule types. Although these two sera were generated against PspAs of different clades, both were equally efficient against all family 1 strains. These results are in accordance with the complement deposition assay, in which both sera were able to increase complement deposition onto pneumococci containing PspA clades 1 and 2. This cross-reactive effect within strains bearing family 1 PspA has been previously reported using anti-PspA1 antibodies [21] and [22]. Moreno et al.

While this does not necessarily address the problems of the

small proportion of primary care consulters with specific back problems (Deyo and Phillips, 1996), it may enable healthcare providers to identify useful areas or sub-groups for intervention which could shift outcomes overall PLX4032 within a primary care population. Given that LBP patients represent a significant proportion of all sufferers in primary care, this is therefore a sensible arena for public health secondary prevention of persistent LBP, and figures such as those presented in this paper can facilitate prioritisation of scarce health resources. KMD is funded through a Research Career Development Fellowship from the Wellcome Trust [083572]. “
“Leonardo C. Clavijo Yinn Cher Ooi and Nestor R. Gonzalez Stroke is the third leading cause of death in developed nations. Up to 88% of strokes are ischemic in nature. Extracranial carotid artery atherosclerotic disease is the third leading cause

of ischemic stroke in the general population and the second most common nontraumatic cause among adults younger than 45 years. This article provides comprehensive, evidence-based recommendations for the management of extracranial atherosclerotic disease, including this website imaging for screening and diagnosis, medical management, and interventional management. Sarah Elsayed and Leonardo C. Clavijo Critical limb ischemia (CLI), the most advanced form of peripheral artery disease (PAD), carries grave implications with regard to morbidity and mortality. Within 1 year of CLI diagnosis, 40% to 50% of diabetics will experience an amputation, and 20% to 25% will die. Management is optimally directed at increasing blood flow to the affected Linifanib (ABT-869) extremity to relieve rest pain, heal ischemic ulcerations, avoid limb loss, and prevent cardiovascular events. This management is achieved by guideline-directed medical

therapy and risk factor modification, whereas the mainstay of therapy remains revascularization by endovascular or surgical means for patients who are deemed potential candidates. Taki Galanis and Geno J. Merli Venous thromboembolism (VTE) is a potentially fatal condition and includes deep vein thrombosis and pulmonary embolism. The novel oral anticoagulants, which include the direct thrombin and factor Xa inhibitors, have been shown to be safe and effective for the treatment of VTE. Additional interventions include thrombolysis and the use of inferior vena cava filters. The purpose of this article is to provide a contemporary review of the treatment of VTE. Jose David Tafur-Soto and Christopher J. White Atherosclerotic renal artery stenosis (RAS) is the single largest cause of secondary hypertension; it is associated with progressive renal insufficiency and causes cardiovascular complications such as refractory heart failure and flash pulmonary edema.