bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of Human Parvovirus 4 VP2 Virus-Like Particles in Yeast and Their Evaluation as an Antigen for Detection of Virus-Specific Antibodies in Human Serum
Authors: Tamošiūnas Paulius Lukas , Simutis Karolis , Kodzė Indrė , Firantienė Regina , Ėmužytė Regina , Petraitytė-Burneikienė Rasa , Žvirblienė Aurelija , Sasnauskas Kęstutis
Published: September 2013

Background: Human parvovirus 4 (PARV4) is a recently discovered member of the Parvoviridae family, which is not closely related to any previously discovered human parvoviruses. PARV4 has been isolated from the plasma of individuals with symptoms of acute viral infection; however, until recently PARV4 had not been associated with any disease, and its prevalence in the human population is yet to be established. Methods: The major capsid protein VP2 of PARV4 was generated in the yeast Saccharomyces cerevisiae and used for serological detection of virus-specific IgG and IgM in the sera of low-risk individuals. Results: One hundred and seventy serum specimens obtained from patients with acute respiratory diseases were tested for PARV4-specific IgG and IgM antibodies. Sixteen individuals (9.4%) were diagnosed as seropositive, including 6 IgM and IgG positive, 6 IgM positive/IgG negative and 4 IgG positive/IgM negative. Seven of the 16 seropositive individuals were between the ages of 3 and 11 with no evidence of parenteral exposure to PARV4 infection. Conclusion: Our data demonstrate that recombinant yeast-derived VP2 protein, self-assembled to virus-like particles, can represent a useful tool when studying the seroprevalence of PARV4 infection. The presence of PARV4-specific antibodies in a low-risk group may indicate the possibility of alternative routes of virus transmission.
Identification, Cloning and Expression of an Insecticide cry8 Gene from Bacillusthuringiensis INTA Fr7-4
Authors: Amadio Ariel F. , Navas Laura E. , Sauka Diego H. , Berretta Marcelo F. , Benintende Graciela B. , Zandomeni Rubén O.
Published: September 2013

Insecticidal activity of Bacillus thuringiensis is attributed largely to the crystal proteins. These were found with specific toxic activity against insects in different orders. A novel cry8 gene from B. thuringiensis strain INTA Fr7-4 from Argentina was characterized. The encoded protein, Cry8Qa2, is 1184 amino acids long and its sequence is more similar to those of Cry8F class. We cloned and expressed the protein in an acrystalliferous strain of B. thuringiensis using two differentially regulated promoters. The recombinant strains produced ovoid crystals with low toxicity against larvae of Anticarsia gemmatalis (Lepidoptera: Noctuidae). The morphology and insecticidal properties of these crystals resembled those produced by the native strain INTA Fr7-4.
Influence of Cochleostomy and Cochlear Implant Insertion on Drug Gradients following Intratympanic Application in Guinea Pigs
Authors: King E.B. , Hartsock J.J. , O'Leary S.J. , Salt A.N.
Published: September 2013

Locally applied drugs can protect residual hearing following cochlear implantation. The influence of cochlear implantation on drug levels in the scala tympani (ST) after round window application was investigated in guinea pigs using the marker trimethylphenylammonium (TMPA) measured in real time with TMPA-selective microelectrodes. TMPA concentration in the upper basal turn of the ST rapidly increased during implantation and then declined due to cerebrospinal fluid entering the ST at the cochlear aqueduct and exiting at the cochleostomy. The TMPA increase was found to be caused by the cochleostomy drilling if the burr tip partially entered the ST. TMPA distribution in the second turn was less affected by implantation procedures. These findings show that basal turn drug levels may be changed during implantation and the changes may need to be considered in the interpretation of therapeutic effects of drugs in conjunction with implantation.
Active Colitis Exacerbates Immune Response to Internalized Food Antigens in Mice
Authors: Cueto-Sola Margarita , Bailon Elvira , Utrilla Pilar , Rodríguez-Ruiz Judith , Garrido-Mesa Natividad , Zarzuelo Antonio , Xaus Jordi , Gálvez Julio , Comalada Mònica
Published: September 2013

Background: Previous studies have indicated that colitis increases intestinal permeability to food antigens. This condition also generates an immunoreactive milieu in the gut, which may exacerbate or counteract allergy reactions. This, along with the fact that both colitis and allergy are being codiagnosed more frequently, means the scientific interest on the immune relation between these pathologies is increasing. We evaluated the immune response to an internalized food antigen that was initiated during a concomitant active intestinal inflammatory response. Methods: An ovalbumin (OVA)-induced immune response was analyzed in healthy mice and in mice suffering from colitis induced by the administration of dinitrofluorobenzene/dinitrosulfonic acid (DNFB/DNS) at the moment of OVA challenge. The OVA-induced clinical score and allergy response both in plasma and in splenocyte cultures from these animals were compared. Results: Although no differences were observed in the allergy clinical score, the concomitant active colitis led to an increase in the immune response to OVA antigen, as shown by increased spleen size and OVA-induced splenocyte proliferation, exacerbated expression of total and OVA-specific IgG1 levels, increased colonic IL-4 expression and OVA-induced IL-4 and IL-5 cytokine expression in spleen cells. Conclusions: Our results indicate that animals with active colitis undergo an exacerbated immune response to an internalized antigen. This finding could be relevant for the allergy management of patients presenting simultaneously with chronic colitis.
The Impact of Exposure to a Novel Female on Symptoms of Infection and on the Reproductive Axis
Authors: Lopes Patricia Castro , Chan Hilary , Demathieu Sophie , González-Gómez Paulina L. , Wingfield John C. , Bentley George E.
Published: September 2013

Background/Aim: Sickness behaviors are the behavioral alterations animals exhibit during the course of an infection, often accompanied by reduced reproductive activity. Adopting sickness behaviors may aid in overcoming the infection, by diverting energy from routine activities towards enhancement of the immune system. Nonetheless, sickness behaviors are plastic, being influenced by specific environmental and social circumstances. Here, we tested whether the presentation of a novel female to males suffering from a simulated infection could impact the behavioral effects of sickness, the reproductive axis, or both. Methods: Male zebra finches were housed in isolation and injected intramuscularly with lipopolysaccharide or saline. Behaviors were recorded before (3 h before injection) and after (3.5 h after injection) addition of a novel female to the cage for 30 min. Four hours after injection, we collected the brain and testis for the analysis of important reproductive axis modulators, gonadotropin-releasing hormone, and gonadotropin-inhibitory hormone, and to quantify gene expression of a proinflammatory cytokine involved in the regulation of sickness behaviors [interleukin (IL)-1β]. Testosterone was quantified in the plasma. Results: The presence of a novel female diminished sickness behaviors and induced alterations in the reproductive axis within 30 min, with no associated changes in brain gene expression of IL-1β. Social environment itself altered brain gene expression of IL-1β. Conclusions: Male zebra finches prioritize the opportunity to mate versus investment in recovery from an infection, as determined by reduced expression of sickness behaviors when a potential mate was present. The behavioral effects of IL-1β appear to be context dependent in this species.
HIV-1 Induces the First Signal to Activate the NLRP3 Inflammasome in Monocyte-Derived Macrophages
Authors: Hernandez Juan C. , Latz Eicke , Urcuqui-Inchima Silvio
Published: September 2013

Background/Aims: Inflammasomes are multimolecular complexes that regulate caspase-1. They act as sensors for endogenous and exogenous signals, and mediate the processing of pro-IL-1β into its secreted, biologically active form. The NLRP3 inflammasome and IL-1β are particularly interesting because they are required for efficient control of viral infections. Indeed, HIV-1 induces expression of NLRP3 and IL-1β in healthy controls, but not in HIV-1-infected patients. Here we evaluate whether HIV-1 can induce activation of the NLRP3 inflammasome. Methods: Human primary monocyte-derived macrophages were infected with HIV-1 in the absence or presence of classical NLRP3 inflammasome activators, and IL-1β release was assessed by ELISA. Results: HIV-1 initiates the priming signal for NLRP3 inflammasome activation through the NF-κB-associated pathway in human primary monocyte-derived macrophages. Furthermore, priming of NLRP3 activation in response to HIV-1 was independent of the viral envelope, since similar results were observed with HIV-1 and pseudotyped HIV-1 lacking the env gene. Conclusion: Our findings suggest that HIV-1 infection promotes IL-1β secretion by inducing the first signal for NLRP3 inflammasome activation, a phenomenon that may contribute to AIDS progression.
hCLCA1 DNA Vaccine Suppresses Cell Hyperplasia and Mucin Expression of Goblet Cells in vitro
Authors: Song L.Q. , Li Y. , Li W.N. , Zhang W. , Yang Y.Q. , Qi H.W.
Published: September 2013

Background: Excessive airway mucus secretion is a remarkable trait of asthma. Mucus overproduction mainly resulted from an increase in goblet cell numbers, which causes considerable damage to health. However, effective therapeutic treatments are still lacking for mucus hypersecretion. Human calcium-activated chloride channel 1 (hCLCA1) has been identified to be predominantly responsible for mucus hypersecretion. Objectives: In this study, we investigated the effects of an hCLCA1 DNA vaccine on the control of mucus production and goblet cell proliferation using an in vitro model goblet cell line (NCI-H292). Methods: The effect of the hCLCA1 DNA vaccine on cell viability and proliferative activity of NCI-H292/hCLCA1 was analyzed by electron microscopy, MTT assay, and flow cytometry. Expression of mucins and MUC5AC, a major member of the mucin gene family in airway goblet cells, was assessed under hCLCA1 DNA vaccine challenges by periodic acid-Schiff staining, quantitative real-time PCR and Western blot, respectively, and the expression profile of granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine in airway inflammation, was also examined by real-time PCR and immunocytochemistry. Results: Results showed that hCLCA1 overexpression caused high cell proliferation and mucin expression, whereas the hCLCA1 DNA vaccine could effectively reverse these abnormal effects. In addition, GM-CSF expression was highly induced by hCLCA1 overexpression and efficiently suppressed by hCLCA1 DNA vaccine. Conclusions: These results illustrate that the hCLCA1 DNA vaccine effectively inhibits cell hyperplasia and mucin gene expression of goblet cells, suggesting that the hCLCA1 DNA vaccine has potential value in the treatment of human asthma.
World Allergy Organization Anaphylaxis Guidelines: 2013 Update of the Evidence Base
Authors: Simons F. Estelle R. , Ardusso Ledit R.F. , Dimov Vesselin , Ebisawa Motohiro , El-Gamal Yehia M. , Lockey Richard F. , Sanchez-Borges Mario , Senna Gian Enrico , Sheikh Aziz , Thong Bernard Y. , Worm Margitta ,   for the World Allergy Organization
Published: September 2013

The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis are a widely disseminated and used resource for information about anaphylaxis. They focus on patients at risk, triggers, clinical diagnosis, treatment in health care settings, self-treatment in the community, and prevention of recurrences. Their unique strengths include a global perspective informed by prior research on the global availability of essentials for anaphylaxis assessment and management and a global agenda for anaphylaxis research. Additionally, detailed colored illustrations are linked to key concepts in the text [Simons et al.: J Allergy Clin Immunol 2011;127:593.e1-e22]. The recommendations in the original WAO Anaphylaxis Guidelines for management of anaphylaxis in health care settings and community settings were based on evidence published in peer-reviewed, indexed medical journals to the end of 2010. These recommendations remain unchanged and clinically relevant. An update of the evidence base was published in 2012 [Simons et al.: Curr Opin Allergy Clin Immunol 2012;12:389-399]. In 2012 and early 2013, major advances were reported in the following areas: further characterization of patient phenotypes; development of in vitro tests (for some allergens) that help distinguish clinical risk of anaphylaxis from asymptomatic sensitization; epinephrine (adrenaline) research, including studies of a new epinephrine auto-injector for use in community settings, and randomized controlled trials of immunotherapy to prevent food-induced anaphylaxis. Despite these advances, the need for additional prospective studies, including randomized controlled trials of interventions in anaphylaxis is increasingly apparent. This 2013 Update highlights publications from 2012 and 2013 that further contribute to the evidence base for the recommendations made in the original WAO Anaphylaxis Guidelines. Ideally, it should be used in conjunction with these Guidelines and with the 2012 Guidelines Update.
Incidental Finding of Isolated Colonic Neurofibroma
Authors: Chelimilla Haritha , Chandrala Chaitanya K. , Niazi Masooma , Kumbum Kavitha
Published: September 2013

Neurofibromatosis is a genetic disorder manifested by characteristic cutaneous lesions called neurofibromas. There are two distinct neurocutaneous syndromes named neurofibromatosis type 1 (also called von Recklinghausen disease or NF1) and neurofibromatosis type 2 (NF2). NF1 is by far the most common presentation and is caused by an autosomal dominant mutation in the NF1 gene mapped to chromosome 17q11.2. The literature shows that gastrointestinal involvement is noted in systemic neurofibromatosis in up to 25% of patients, but isolated intestinal neurofibromatosis is a very rare manifestation. We herein present the case of a 70-year-old woman who was diagnosed with an isolated colonic neurofibroma without any systemic signs of neurofibromatosis; only a few case reports of this condition have been published to date.
Crosstalk between platelets and the complement system in immune protection and disease
Authors: Langer Harald F. , Verschoor Admar
Published: September 2013

Platelets have a central function in repairing vascular damage and stopping acute blood loss. They are equally central to thrombus formation in cardiovascular diseases such as myocardial infarction and ischaemic stroke. Beyond these classical prothrombotic diseases, immune mediated pathologies such as haemolytic uraemic syndrome (HUS) or paroxysmal nocturnal haemoglobinuria (PNH) also feature an increased tendency to form thrombi in various tissues. It has become increasingly clear that the complement system, part of the innate immune system, has an important role in the pathophysiology of these diseases. Not only does complement influence prothrombotic disease, it is equally involved in idiopathic thrombocytopenic purpura (ITP), an autoimmune disease characterised by thrombocytopenia. Thus, there are complex interrelationships between the haemostatic and immune systems, and platelets and complement in particular. Not only does complement influence platelet diseases such as ITP, HUS and PNH, it also mediates interaction between microbes and platelets during systemic infection, influencing the course of infection and development of protective immunity. This review aims to provide an integrative overview of the mechanisms underlying the interactions between complement and platelets in health and disease.
Cardiovascular and upper gastrointestinal bleeding consequences of low-dose acetylsalicylic acid discontinuation
Authors: Soriano Lucía Cea , Bueno Héctor , Lanas Angel , Rodríguez Luis A. García
Published: September 2013

It was the aim of this study to investigate whether low-dose acetylsalicylic acid (ASA) therapy for secondary cardiovascular prevention should continue, despite the risk of gastrointestinal bleeding. We aimed to make a clinically meaningful benefit–risk assessment regarding the cardiovascular and gastrointestinal consequences of ASA discontinuation. This case–control study used The Health Improvement Network UK primary care database to identify patients aged 50–84 years during 2000–2007 with a first ASA prescription for secondary cardiovascular prevention (N = 39,513). New cases of non-fatal myocardial infarction (MI)/coronary death (n = 1,222), ischaemic stroke (IS)/transient ischaemic attack (TIA) (n = 673) and upper gastrointestinal bleeding (UGIB) (n = 169) were identified after a mean follow-up of 3.2, 3.4 and 4.0 years, respectively. ASA discontinuers before the index date were identified. Attributable risks associated with ASA discontinuation were calculated and National Institute for Health and Clinical Excellence annual economic data were used to estimate healthcare costs. The cumulative incidences of non-fatal MI/coronary death, IS/TIA and UGIB among ASA discontinuers within the first year of follow-up were 17, 11 and 1.6 per 1,000 persons, respectively. This corresponds to eight extra cardiovascular events, and a reduction of 0.4 UGIB events per year compared with current ASA users. Extrapolating to the UK population aged over 50 years, avoiding discontinuation of ASA could prevent 12,786 coronary and 7,672 cerebrovascular events/year, at the expense of 1023 extra UGIB events, saving approximately £100 million/year. In conclusion, preventing patients with cardiovascular disease from discontinuing ASA could result in substantial clinical and economic gains.
Ouabainlike Na+,K+-ATPase inhibitor in the plasma of normotensive and hypertensive humans and rats.
Authors: de Wardener H E , Millett J , Holland S , MacGregor G A , Alaghband-Zadeh J
Published: September 2013

Acute volume expansion, increased sodium intake, and restraint on sodium excretion endow the plasma with an increased capacity to inhibit sodium transport. Cytochemical techniques can detect the presence of Na+K+-adenosine triphosphatase (ATPase) inhibitor in the plasma of normal humans and rats, the concentration of which is controlled by salt intake. The substance responsible appears to originate in the hypothalamus, where the concentration is also controlled by salt intake. The plasma concentration of the cytochemically detectable Na+,K+-ATPase inhibitor is substantially raised in the plasma of patients with essential hypertension, spontaneously hypertensive rats (SHR) and of Milan hypertensive rats. The concentration of activity in the hypothalamus of SHR is also considerably raised. These findings demonstrate that these forms of hypertension are associated with a rise in the concentration of a cytochemically detectable circulating Na+,K+-ATPase inhibitor that under normal circumstances is controlled by salt intake.
Regulation of Na+, K+-ATPase by the endogenous sodium transport inhibitor from hypothalamus.
Authors: Haupert G T
Published: September 2013

We characterized the effect of a small, nonpeptidic molecule isolated from bovine hypothalamus on mammalian Na+, K+-adenosine triphosphatase (ATPase). This hypothalamic factor has been shown to inhibit ATPase activity of purified dog kidney enzyme reversibly with high affinity. This report reviews the mechanism of inhibition. Hypothalamic factor inhibits Na+, K+-ATPase only from the extracellular surface. It prevents the phosphorylation from magnesium and inorganic phosphate of the active site aspartate residue of Na+, K+-ATPase and stabilizes the enzyme in an E2 conformation, preventing a sodium-induced shift from E2 to E1. Binding and dissociation reactions of hypothalamic factor in cultured renal tubular epithelial cells show a time frame different from that in isolated membranes and consistent with physiological relevance. A possible mechanism for the physiological regulation of Na+, K+-ATPase, including a cycle of binding and rapid dissociation in intact renal tubular cells, is discussed.
Endogenous digitalislike compounds. A tentative update of chemical and biological studies.
Authors: Cloix J F
Published: September 2013

Endogenous digitalislike compound (or compounds) has been described as involved in some diseases. Questions remain concerning its chemical nature, origin, and biological properties. The methods of measuring the compound are based on biological properties of digitalis, mainly Na+, K+-adenosine triphosphatase (ATPase) inhibition and related properties. Chemically, digitalislike compound has been described as a peptide, as fatty acids, and as a steroid. Its origin could be the brain, particularly the hypothalamus and pituitary gland. The adrenal glands were also proposed as its origin. The reported biological properties of digitalislike compound are mainly dependent on Na+, K+-ATPase inhibition. No definitive conclusions can be drawn from the available data.
In vivo release of angiotensin II from the rat hypothalamus.
Authors: Brosnihan K B , Schiavone M T , Sprunger A E , Chappell M C , Rizzo M , Ferrario C M
Published: September 2013

Recent studies suggest that angiotensin II is released from neuronal tissue in vitro, but the occurrence of this phenomenon in the intact brain has not yet been demonstrated. To characterize the in vivo release of immunoreactive angiotensin II, push-pull cannulas were positioned in the anterior hypothalamus in 47 Sprague-Dawley rats (200-250 g) anesthetized with Inactin (100 mg/kg i.p.). Artificial cerebrospinal fluid was perfused at 20 microliters/min, and effluent samples were collected for 15-minute periods over 2 hours. Angiotensin II was detectable (greater than 2.5 pg/ml) in the push-pull cannula perfusate of the majority (76%) of the rats. Spontaneous release of immunoreactive angiotensin II was constant for 2 hours in 11 rats at values averaging from 4.4 +/- 1.5 to 8.2 +/- 2.2 pg/ml. In addition, bilateral nephrectomy performed 48 hours before did not affect the detection of angiotensin II (n = 3). Angiotensin immunoreactivity in the rat hypothalamus was further characterized by high performance liquid chromatography. The analysis showed that the perfusate contained authentic angiotensin II as well as other angiotensin metabolites. The effect of beta-adrenergic modulation on the release of angiotensin II was assessed in 20 rats by adding isoproterenol (10(-10), 10(-8), and 10(-6) M), propranolol (10(-6) M), or a combination of both. Neither activation nor inhibition of hypothalamic beta-receptors altered the spontaneous release of angiotensin II. These data demonstrate that angiotensin II and congener peptides are detectable in the microenvironment of the anterior hypothalamus of the anesthetized rat and that the release of angiotensin II immunoreactivity in the anterior hypothalamus is not modified by beta-adrenergic receptors.
Tidal volume affects the response to inactivation of the rostral ventrolateral medulla.
Authors: Cox B F , Brody M J
Published: September 2013

During preliminary studies of the rostral ventrolateral medulla as a relay site for responses activated from forebrain, loss of the marked depressor effect of lidocaine, microinjected into lateral rostral ventrolateral medulla, was observed when rats were ventilated spontaneously rather than by artificial ventilation. The mechanism of this effect was studied in rats ventilated at a tidal volume of 2.5 ml. Bilateral injection of 4% lidocaine into lateral rostral ventrolateral medulla decreased mean arterial pressure by -47 +/- 8 mm Hg and heart rate by -68 +/- 21 beats/min. Reduction of tidal volume to 1.5 ml significantly attenuated the fall in mean arterial pressure and heart rate produced by lidocaine to -17 +/- 11 mm Hg and -12 +/- 8 beats/min. The decrease in tidal volume resulted in decreased arterial PO2 and pH, and increased PCO2. However, the depressor effect of lidocaine was not significantly affected by independently changing PO2 and PCO2. The physical stimuli associated with reduction of tidal volume (i.e., changes in lung inflation and chest wall movement) appeared to mediate the attenuated depressor response to the injection of lidocaine into the lateral rostral ventrolateral medulla. These data suggest that 1) tonic vasomotor activity derived from lateral rostral ventrolateral medulla is strongly influenced by altered mechanics of respiration, and 2) the anatomical location of the putative vasomotor center may not be defined by the lateral rostral ventrolateral medulla under all conditions.
Clinical implications of primary aldosteronism with resistant hypertension.
Authors: Bravo E L , Fouad-Tarazi F M , Tarazi R C , Pohl M , Gifford R W , Vidt D G
Published: September 2013

Twenty-eight patients with resistant hypertension were found to have primary aldosteronism; 25 had solitary adenoma and 3 had adrenal hyperplasia. All were severely hypertensive despite receiving three or more antihypertensive agents, including conventional doses of diuretics, sympatholytics, and vasodilators. Hypervolemia (24 patients) or normovolemia (2 patients) despite severe diastolic hypertension was the hallmark in 26 patients. Adequate salt and water depletion alone with spironolactone (200 mg/day) and hydrochlorothiazide (50-100 ng/day) reduced arterial pressure in all. Twenty-two patients had surgical removal of a solitary adenoma. Over 1 to 2 years of follow-up, 13 were normotensive without medication, and six required hydrochlorothiazide and three hydrochlorothiazide plus a beta-blocker to normalize blood pressure. Blood pressure response to surgery had no relation to either duration or severity of hypertension. Six patients (three with hyperplasia, three with adenoma) have continued diuretic therapy and are normokalemic and normotensive. These results indicate that primary aldosteronism can be associated with sever and drug-resistant hypertension, that maintained hypervolemia is the reason for resistance to therapy, that sustained volume depletion is the most important therapeutic goal for these patients, and that cure can be achieved despite prolonged and severe hypertension.
Atrial natriuretic factor in essential hypertension and adrenal disorders.
Authors: Sugawara A , Nakao K , Kono T , Morii N , Yamada T , Itoh H , Shiono S , Saito Y , Mukoyama M , Arai H
Published: September 2013

Patients with untreated essential hypertension had significantly higher plasma atrial natriuretic factor (ANF) levels (92.9 +/- 12.9 pg/ml, mean +/- SE) than those of age-matched controls (37.8 +/- 6.0 pg/ml; p less than 0.01). Plasma ANF levels in essential hypertensive patients showed a significant positive correlation with mean arterial pressure (MAP; r = 0.46, p less than 0.05) and an inverse correlation with plasma renin activity (PRA; r = -0.43, p less than 0.05). Plasma ANF levels after medication showed significant correlation with the decrease in MAP (r = 0.565, p less than 0.05). Patients with primary aldosteronism had significantly higher plasma ANF levels (122.4 +/- 30.2 pg/ml, n = 8) than those of controls (p less than 0.05). The levels returned to normal after extirpation of adrenal tumors. The response of plasma ANF levels in patients with primary aldosteronism to volume expansion with infusion of 2 L of physiological saline in 2 hours was greater than in controls. Such exaggerated response disappeared after surgical treatment. Infusion of angiotensin II (Ang II; 20 ng/kg/min) or norepinephrine (200 ng/kg/min) for 30 minutes to normal volunteers (n = 5) resulted in a rise in MAP (24.9 +/- 3.3 and 15.8 +/- 4.4 mm Hg, respectively) and a twofold increase in plasma ANF level. Infusion of the Ang II antagonist [Sar1, Ile8]Ang II (600 ng/kg/min) for 30 minutes, resulted in a rise in MAP (18.8 +/- 2.1 mm Hg) and more than a twofold increase in plasma ANF level in patients with essential hypertension (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
Pindolol, not propranolol, reverses cardiac hypertrophy in renal hypertensive rats.
Authors: Saragoça M A , Cezaretti M L , Tavares A , Bessa A M , Almeida J B , Amorin M P , Ramos O L
Published: September 2013

Reversal of cardiac hypertrophy has been obtained by treatment with some antihypertensive drugs but has not been achieved consistently with beta blockers. To investigate whether this difference might be explained by the distinct hemodynamic actions of the drugs, we studied the effects of propranolol and pindolol, beta blockers with distinct modes of action, on cardiac hypertrophy of hypertensive male Wistar rats, two-kidney, one clip (2K1C) Goldblatt model (n = 33) and sham-operated control rats (n = 34). We also assessed the effects of such therapies on the ventricular pumping ability during open-chest, transient aortic occlusion. Four weeks after surgery, propranolol (5 mg/kg/day p.o.) was given to hypertensive (n = 8) and control rats (n = 11); pindolol was also given orally (1 mg/kg/day) to similar groups (n = 7 and n = 5, respectively). Untreated animals served as controls for both groups. Cardiac hypertrophy developed with hypertension in the untreated rats of the propranolol (3.38 +/- 0.18 vs 2.60 +/- 0.08 mg/g; p less than 0.01) and pindolol groups (3.93 +/- 0.21 vs 2.40 +/- 0.03 mg/g; p less than 0.001). Treatment reversed cardiac hypertrophy in the pindolol-treated (3.01 +/- 0.19 vs 3.93 +/- 0.21 mg/g; p less than 0.001, NS) but not in the propranolol-treated rats (3.24 +/- 0.18 vs 3.38 +/- 0.21 mg/g, NS). The maximal pressure that developed during aortic occlusion in the propranolol group was similar to that observed in the pindolol group. These results indicate that cardiac hypertrophy is reversed by pindolol but not by propranolol, and that this reversal does not interfere with left ventricular pumping ability.
Oral contraceptives and hypertension.
Authors: Woods J W
Published: September 2013

Oral contraceptives result in a mild elevation of blood pressure in most women and overt hypertension in about 5%. Both estrogen and progestogen are responsible for the blood pressure effect, but the mechanism is as yet unknown. The risk of cardiovascular complications is found primarily in women over 35 years of age and in those who smoke. Preparations with an estrogen content of 30 g and a progestogen content of 1 mg or less appear to be safe.
Hypertension, antihypertensive treatment, and sudden coronary death. The Framingham Study.
Authors: Kannel W B , Cupples L A , D'Agostino R B , Stokes J
Published: September 2013

During 30 years of follow-up, there were 183 sudden deaths in men and 77 in women ages 35 to 94 years who participated in the Framingham Study. Risk of sudden death was increased threefold in hypertensive persons but only if there was no previously diagnosed coronary heart disease. Men receiving antihypertensive treatment had more than twice the risk of sudden death compared with those who were untreated, whether or not they had prior manifestations of coronary heart disease. More than twice as many men who died suddenly were receiving antihypertensive therapy compared with those in the population at risk of the same age. In those with overt coronary heart disease, 34% of those dying suddenly were on antihypertensive treatment compared with 18% of those of the same age in the general population. Multivariate analysis taking into account the level of blood pressure, electrocardiographic abnormalities, and previously diagnosed coronary heart disease and cardiac failure, all of which are predisposing factors for sudden death, indicated a persistent increased risk of sudden death in association with antihypertensive treatment. Tests of interaction indicate that the excess sudden death risk was not confined to those with electrocardiographic abnormalities. In women, it may be associated with diabetes. These data suggest that some feature of antihypertensive treatment as practiced in the general population may contribute to sudden death incidence in an ill-defined subgroup of hypertensive persons.
Compliance and blood pressure control.
Authors: Klein L E
Published: September 2013

Compliance with medical therapy in general is often low, and compliance with blood pressure treatment is no better. Numerous studies have shown that patients frequently drop out of treatment for hypertension. Furthermore, even when patients stay in treatment, they often take their medications in a way quite dissimilar from that prescribed. Identifying noncompliant patients is important but not always easy to accomplish. Pill counts, the "gold standard," are seldom practical in routine clinical practice. Assessing compliance by its biological effect is compromised by physiological diversity among patients. Assessing compliance from patient self-reports is limited in its accuracy but is more useful than many researchers and clinicians appreciate. Compliance behavior is affected by many factors. Complexity of medical regimen has some effect; the presence of drug side effects has surprisingly little. Contrary to what many clinicians think, increased age is often accompanied by increased medication compliance. Features of the doctor-patient relationship likely have an important effect on patient compliance, though our knowledge of these factors is still limited.
Preferential noradrenergic innervation of alpha-adrenergic receptors in vascular smooth muscle.
Authors: Langer S Z , Shepperson N B , Massingham R
Published: September 2013

In the isolated perfused hindlimb preparation of the dog, pressor responses to norepinephrine (NE) are mediated by postsynaptic alpha 1- and alpha 2-adrenergic receptors. Results obtained using preferential alpha 1- and alpha 2-adrenergic receptor antagonists suggest that the alpha 1-subtype is predominantly innervated while both alpha 1- and alpha 2-adrenergic receptor subtypes in vascular smooth muscle are accessible to circulating agonists and antagonists. Preliminary studies in the isolated perfused cat spleen support these in vivo findings in the dog. In contrast to vascular smooth muscle, the cat nictitating membrane appears to contain only alpha 1-adrenergic receptors postsynaptically.
Aortic endothelial and subendothelial cells in experimental hypertension and aging.
Authors: Haudenschild C C , Prescott M F , Chobanian A V
Published: September 2013

The endothelial and subendothelial cellular changes occurring as a result of hypertension and aging were characterized in deoxycorticosterone/salt-treated (D/S), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats. An increase in the number of subendothelial cells occurred with both hypertension and aging and was most dramatic with D/S hypertension. Many of the cells found in the widened subendothelium showed morphological characteristics of mononuclear cells (both macrophages and lymphocytes), and of smooth muscle cells. Normalization of blood pressure by withdrawal of D/S and maintenance of rats on a low salt diet reversed the number of subendothelial cells to levels of control animals of comparable age. Significant alterations were seen in the aortic endothelial cells of D/S animals. Within 2 to 4 weeks of D/S administration, the endothelial cells doubled in number and often assumed bizarre shapes with nuclear folding and bulging toward the lumen. Some similar abnormalities in endothelial cell shape and appearance occurred with increasing age in the SHR and control WKY, although the number of endothelial cells increased only slightly in these groups. These results suggest that profound cellular changes in the aortic intima occur with an increase in blood pressure. These changes are pronounced in the D/S model of hypertension, while virtually absent in SHR. Comparable alterations also may be seen in aged normotensive animals, but to a lesser extent and with slower progression.
Disturbances of calcium metabolism in the spontaneously hypertensive rat.
Authors: McCarron D A , Yung N N , Ugoretz B A , Krutzik S
Published: September 2013

Ionized calcium is critical to the maintenance of normal cardiovascular function. Recently, vasoactive properties have also been attributed to parathyroid hormone (PTH). The present study characterizes the calcium-PTH axis in the spontaneously hypertensive rat (SHR) in order to determine the effects of chronic alterations in calcium intake on the development and maintenance of hypertension in this species. Thirty-six SHR and 36 Wistar-Kyoto (WKY) normotensive control rats were studied. The rats were fed one of three levels (percent of total diet) of calcium (normal 0.5%, low-normal 0.25%, high 4.0%) beginning at 10 weeks of age. Serum total and ionized calcium, serum PTHs, urinary electrolytes, and systolic blood pressures were assessed by repeated measurements between 10 and 48 weeks of age. Irrespective of calcium intake, the SHRs had lower serum ionized calcium concentrations (p less than 0.001) and higher PTH levels (p less than 0.001) than the WKYs. Serum total calcium were similar for the two strains. Urinary calcium excretion was greater in the SHR (p less than 0.001) relative to the WKY. The high (4.0%) calcium diet normalized the serum ionized calcium and attenuated the development of the SHRs' hypertension (p less than 0.001). The present study describes several previously unrecognized abnormalities of calcium metabolism in the SHR. These disturbances may be of pathogenetic importance in the development and maintenance of hypertension in the SHR.
Effect of prolonged dietary administration of vanadate on blood pressure in the rat.
Authors: Steffen R P , Pamnani M B , Clough D L , Huot S J , Muldoon S M , Haddy F J
Published: September 2013

Vanadate, a potent naturally occurring Na+,K+-ATPase inhibitor thought to have a role in regulating Na+-K+ pump activity, was fed to uninephrectomized rats drinking tap water or a 1% solution of sodium chloride for as long as 56 weeks. Feeding was achieved by adding sodium orthovanadate to normal rat chow equivalent to 100 or 200 ppm vanadium by weight. In the rats drinking tap water, systolic pressure gradually increased over a period of several weeks and then was sustained in a dose-related manner for the duration of the treatment. The increased pressure was not associated with changes in water intake, urine output, or urinary sodium excretion but correlated positively with plasma vanadium levels ranging from 0.04 to 0.27 microgram/ml. Increased pressure was associated with increased heart-to-body-weight ratio but did not appear to occur in a small group of animals drinking the 1% solution of sodium chloride. These findings, considered in the light of others, indicate that vanadate deserves continued study in relation to hypertension.
Antihypertensive effect of orally administered glandular kallikrein in essential hypertension. Results of double blind study.
Authors: Overlack A , Stumpe K O , Kolloch R , Ressel C , Krueck F
Published: September 2013

The antihypertensive effect of oral administration of pig pancreatic kallikrein was investigated in a double blind study of 20 patients with essential hypertension. Kallikrein treatment lowered the blood pressure (BP) significantly from 159.5/104.5 to 146.3/92.8 mm Hg in the supine and from 153/106.1 to 136.1/95.6 mm Hg in the standing position. Blood pressure remained unchanged in the placebo group. Urinary kallikrein, sodium excretion, and GFR increased with treatment, but these changes did not reach statistical significance, In the kallikrein-treated patients but not in the placebo group, urinary kallikrein was correlated both to GFR (r = 0.7, p less than 0.001) and sodium excretion (r = 0.5, p less than 0.01). The antihypertensive mechanism of kallikrein treatment remains unknown. It could be speculated that kallikrein may induce changes in local blood flow, mediated by kinin and prostaglandin release.
Detection and isolation of inactive, large molecular weight renin in human kidney and plasma.
Authors: Atlas S A , Sealey J E , Dharmgrongartama B , Hesson T E , Laragh J H
Published: September 2013

Estimation of apparent molecular weight (mw) of inactive renin by gel filtration of human plasma was found to be inaccurate when "acid activation" or "cryoactivation" was used for detection; recoveries were only 5% to 20%. Trypsin activation produced greater recoveries, but the apparent elution volume of inactive renin varied with the concentration of trypsin used; the presence of trypsin inhibitors increased trypsin requirements to 100 to 200 micrograms/ml in the 60,000 dalton region, while low protein concentration in the 50,000 dalton region resulted in destruction of renin by as little as 10 microgram/ml trypsin. A composite trypsin-activated inactive renin peak corresponded to a mw of 56,000 +/- 1500 daltons (104% to 120% recovery), while active plasma renin was 48,000 +/- 2000 daltons. When this prorenin-like substance was isolated by affinity chromatography, it was found to be completely inactive. It was also nearly free of trypsin inhibitors, so that a single trypsin concentration correctly identified and confirmed the elution characteristics of inactive renin peak following gel filtration. The apparent mw of trypsin-activated inactive renin was slightly lower (52,000 daltons) than that of inactive renin. Human renal cortex was also found to contain a trypsin-activable form of renin. Like plasma inactive renin, it could be isolated by chromatography on Cibacron blue-agarose (Affi-Gel blue). It was found to be completely inactive following passage over a pepstatin affinity column. This inactive renal renin, as well as a similar substance in perfusate of normal human kidney, had a mw of 49,500 +/- 1000, while active renal renin was 39,500 +/- 500. Trypsin-activated inactive renal renin had a mw of 46,500 +/- 500; its pH optimum was identical with that of active renal renin, and it no longer bound to Cibacron blue-agarose. We conclude that both human plasma and kidney contain an inactive, prorenin-like substance that can be detected reliably by trypsin activation. There appear to be slight differences in the apparent mw of plasma renins and kidney renin, but the similarity of other characteristics suggests that the inactive, prorenin-like substances in renal cortex, renal perfusate, and plasma may be one and the same substance.
Sequential renal hemodynamics in experimental benign and malignant hypertension.
Authors: Dzau V J , Siwek L G , Rosen S , Farhi E R , Mizoguchi H , Barger A C
Published: September 2013

To examine the sequential renal hemodynamic changes in experimental renovascular hypertension, the uninephrectomized dog was studied immediately after renal artery constriction, throughout chronic benign hypertension, and during malignant hypertension. Intrarenal resistance fell immediately after renal artery constriction, but rose above control within hours. Intrarenal infusion of teprotide resulted in vasodilatation during the first 3 days but failed to do so during the chronic phase of benign hypertension. During the transition from benign to malignant hypertension, angiotensin II-dependent renal vasoconstriction developed associated with natriuresis, plasma volume contraction and a vicious cycle of hyperreninemia and severe vascular damage.
Regulation of aldosterone biosynthesis during sodium deficiency. Evidence for an essential role of the pituitary gland.
Authors: McCaa R E , Langford H G , Montalvo J M , Andy O J , Read V H , McCaa C S
Published: September 2013

The aldosterone response to adrenocorticotropic hormone (ACTH) and angiotensin II (AII) was evaluated in patients with pituitary insufficiency before and after dietary sodium restriction (10 mEq Na+/day for 12 days). On normal sodium intake, plasma aldosterone concentration and plasma cortisol concentration failed to change from control levels in response to a single injection of ACTH or to a continuous 1-hour infusion of AII in patients with pituitary insufficiency. In response to dietary sodium restriction for 12 days, plasma renin activity (PRA) increased fivefold in patients with pituitary insufficiency, while plasma aldosterone concentration failed to increase significantly, averaging 11.0 +/- 3.1 before and 12.3 +/- 3.7 ng/dl (ns, p greater than 0.05) after sodium deficiency. Although aldosterone secretion failed to increase during sodium deficiency, the patients came into balance at 10 mEq without a significant change in arterial blood pressure (BP). In sharp contrast to the lack of aldosterone response to ACTH before sodium deficiency, plasma aldosterone concentration increased markedly from 12.9 +/- 3.3 to 156 +/- 17.3 ng/dl (p less than 0.001) in response to ACTH after sodium deficiency. Although the adrenal glomerulosa cells were markedly sensitive to ACTH during sodium deficiency, they remained almost totally refractory to AII since aldosterone secretion failed to increase significantly in response to continuous infusion of a pressor dose of AII for 1 hour. Replacement therapy with ACTH gel for 3 months in patients with pituitary insufficiency failed to restore a normal aldosterone response to either ACTH or AII. These data demonstrate that some non-ACTH pituitary factor(s) is essential for a normal aldosterone response to ACTH, AII, and sodium deficiency.
Localization, purification, and biological activity of a new aldosterone-stimulating factor.
Authors: Sen S , Valenzuela R , Smeby R , Bravo E L , Bumpus F M
Published: September 2013

An aldosterone-stimulating factor (ASF) has been isolated from normal human urine and found to be a glycoprotein with a molecular weight of 26,000 daltons. ASF stimulated aldosterone production both in vivo and in vitro. ASF was found to be different from other known aldosterone secretogogues by the use of high performance liquid chromatography (HPLC). The retention time of ASF was different (17.0 minutes) from ACTH (retention time, 28.4 minutes), beta-lipotropin (retention time, 20.5 minutes), and angiotensin II. Proteolytic enzyme digestion and purification of ASF by HPLC yielded a smaller molecule (retention time, 22.0 minutes) with a molecular weight of 4000 daltons. This smaller molecule also stimulated aldosterone production in vitro. This showed that the structural requirement for steroidogenesis may be residing in a smaller molecule. ASF failed to produce hypertension in adrenalectomized rats. By immunofluorescence (using fluorescein conjugated antibodies), ASF was found to be localized in the anterior lobe of the pituitary gland. Data suggest that ASF, a new aldosterone-stimulating hormone that has not been described before, is secreted by the pituitary gland, and the adrenal gland appears to be the target organ for the biological activities.