Four analogs of the natural macrophage-activator peptide tuftsin (T-K-P-R) were synthesized with the aim of obtaining compounds more effective in the stimulation of the immune system than tuftsin. Modifications to the parent tuftsin molecule were (i) substitution of the proline (P) residue, and/or (ii) replacement of the N-terminal residue threonine (T). The study presented here shows that the integrity of the NH2 terminus is not mandatory for a full biological tuftsin-like activity. Our data also suggest that the analogue F-(psi)-K-ABO-R, where ABO is a non-natural amino acid, is a promising agent for immunotherapy of infectious and neoplasic diseases for which tuftsin has already demonstrated some efficacy.

Amino Acid Sequence↗

PubMedDate not supplied

Specific decrease of secretin/VIP-stimulated adenylate cyclase in the heart from the Lyon strain of hypertensive rats.

The cardiac adenylate cyclase activity of genetically hypertensive rats from the Lyon strain (LH) was compared to that of Lyon normotensive rats (LN) and that of low blood pressure Lyon rats (LL). The major finding was a 30-35% decrease of secretin- and VIP-stimulated adenylate cyclase activity in cardiac membranes of LH rats that was already obvious in 5 week-old prehypertensive animals: this alteration was apparently specific for the cardiac secretin/VIP-stimulated adenylate cyclase activity, the same activity in membranes from brain, anterior pituitary, and liver being similar in LH, LN and LL rats. It is tempting to conclude that a selective alteration of functional cardiac secretin/VIP receptors in LH rats reflects a local hyperactivity of the sympathetic adrenergic system.

Adenylyl Cyclases↗

PubMedDate not supplied

Myofibroblast: a prognostic marker and target cell in progressive renal disease.

Myofibroblasts play an important role in many tissue injuries, and particularly in renal disease. The myofibroblast differentiation is an early event in the development of fibrosis. Myofibroblast-like cells express smooth muscle (SM) cytoskeletal markers (alpha-SM actin in particular) and participate actively in the production of extracellular matrix. Identification of early risk factors, particularly histological criteria, could be useful to identify patients at risk of progressive renal failure and needing a treatment. The evaluation of myofibroblast differentiation in renal tissue may reflect the intensity of tissue injury, predict long term outcome of chronic renal disease and help physicians to select therapeutic choices. More than a disease activity indicator. myofibroblasts appear to be a pivotal target for future therapies in progressive renal disease.

Biomarkers↗

PubMedDate not supplied

Plasma lipids in genetically hypertensive rats of the Lyon strain.

Of the four standardized strains of genetically hypertensive rats, only the Lyon hypertensive rats spontaneously exhibit a higher body weight than their normotensive controls. In order to determine if this increased body weight is associated with alterations in the lipid metabolism, plasma triglycerides (TG), phospholipids (PL), total cholesterol (TPC), and high-density lipoprotein cholesterol (CHDL) were followed in Lyon hypertensive (LH), normotensive (LN), and hypotensive (LL) male rats between 5 and 32 weeks of age. TG were stable with age in LL and LN but increased in LH rats. PL decreased in LL, remained stable in LN, but increased with age in LH rats. TPC and CHDL were stable in LL and LN and increased with age in LH rats. Plasma lipids were not related to the blood pressure level, but were positively related to the body weight in the hypertensive strain. Thus, starting at the age of 5 weeks, LH rats exhibit spontaneously a significant increase in blood pressure, body weight, and plasma lipid concentrations.

Aging↗

PubMedDate not supplied

Purification of developmentally regulated avian 400-kDa intermediate filament associated protein. Molecular interactions with intermediate filament proteins and other cytoskeleton components.

IFAPa-400, a 400-kDa developmentally regulated protein thought to be associated with intermediate filaments, has been purified from chick embryo hearts to investigate its interaction with vimentin and other IF proteins and to identify other cellular components to which this cytoskeletal protein associates. Previous studies suggested that this protein was associated with the vimentin-containing intermediate filament lattice of myoblasts and neuroblasts before their terminal differentiation, providing these cells with a particular intermediate filament cytoskeleton that could satisfy specific mechanical requirements during their intense morphogenetic activities. Although IFAPa-400 partially reassociated with vimentin and desmin in disassembly-reassembly experiments using crude IF preparations from chick embryo hearts, in vitro recombination of purified IFAPa-400 with vimentin and desmin failed to demonstrate any direct association. When purified IFAPa-400 was used as a probe in blot overlay assays, however, specific binding to vimentin and desmin was observed, providing the first evidence of a physical association between IFAPa-400 and intermediate filament proteins. The blot overlay experiments also demonstrated that IFAPa-400 binds to two unidentified polypeptides of 19 and 32 kDa. These results are thus consistent with the hypothesis that a structural lattice requiring a vimentin-IFAPa-400 combination constitutes the intermediate filament system of myogenic and neurogenic cells.

Animals↗

PubMedDate not supplied

Urinary prostaglandins in the Lyon strains of hypertensive, normotensive, and low blood pressure rats.

A longitudinal study of the urinary excretion of prostaglandins (PGs) E and F alpha was performed in simultaneously selected hypertensive (LH), normotensive (LN), and low blood pressure (LL) female rats of the Lyon strains aged from 5 to 45 weeks. The urinary excretion of PGE did not significantly differ between LL and LN rats whereas in LH rats it was found to be significantly lower than that of LN or LL rats starting at the age of 32 weeks. The urinary excretion of PGF alpha was significantly reduced in both LL and LH rats; however, this decrease was more marked in LH than in LL animals and, from 9 weeks of age, the urinary PGF alpha were significantly lower in LH than in age-matched LL rats. In addition, both PGE and PGF alpha were found to be significantly and negatively related to the systolic blood pressure level in LH rate (r = -0.56, n = 58, p less than 0.001 for PGE; and r = -0.78, n = 58, p less than 0.001 for PGF alpha) but not in LN of LL animals. In conclusion, it seems unlikely that renal PGs could play a primary role in the spontaneous hypertension observed in the Lyon strain of rats.

Animals↗

PubMedDate not supplied

Genetics of blood pressure and associated phenotypes in the Lyon rat.

The Lyon model of genetic hypertension is made of 3 simultaneously selected strains, one hypertensive (LH) one normotensive (LN) and one with low blood pressure (LL). Since LN and LL rats exhibit the same blood pressure (BP) LH rats can be compared to 2 genetically pure and different strains of control animals. This proved to be useful for the interpretation of the data of molecular genetic studies, eg: since the renin gene was polymorphic between LH and LN but not between LH and LL rats it could be suggested that the reported linkage of renin gene polymorphism and high BP in F2 hybrids may involve another closely located gene. LH rats associate to high BP spontaneous increases in body weight, plasma cholesterol, fibrinogen and hematocrit. During the phenotyping of F1 and F2 hybrids from a LH x LN cross and of back-crosses to LH rats it was observed that all these phenotypes were recessive, except the large body weight of LH rats which was dominant and, thus, unrelated to BP. On the contrary, BP was significantly related to plasma cholesterol in both F2 and back-cross rats and, in this latter cohort, plasma cholesterol correlated also with fibrinogen and hematocrit levels. Therefore, the study of the Lyon rat may be useful not only to determine the genes involved in hypertension but also those which contribute to other cardiovascular risk factors such as elevated fibrinogen and hematocrit.

Animals↗

PubMedDate not supplied

A pilot study demonstrating clinical benefit from intralesional interferon alpha 2B in the treatment of Peyronie's disease.

Intralesional therapy is a less invasive method for the treatment of Peyronie's disease. The objective of this study was to evaluate intralesional injections of interferon alpha 2B (IFN-alpha-2B) as an effective alternative to the surgical treatment of Peyronie's disease. Twenty-one patients with Peyronie's disease were evaluated by use of penile duplex Doppler ultrasonography for cavernosal blood flows, degree of penile curvature, and plaque size. A questionnaire was given to all patients to assess sexual function. Each patient then received biweekly intralesional injections of 1 x 10(6) units of IFN-alpha-2B in 10 ml of normal saline over a period of 6 months. There was no placebo control group in this study. At the conclusion of the study, penile duplex Doppler imaging was repeated. A questionnaire was completed by all patients to assess changes in sexual function after treatment. Twenty patients completed the study, with all men reporting subjective softening of their plaques. Nine of 10 patients initially reporting penile pain with erection (90%) had resolution of their phallalgia while on study protocol. Thirteen patients (65%) had significant improvement in curvature, ranging from 20 to 90%. Seventeen patients (85%) demonstrated an objective 10 to 80% decrease in plaque size. Biweekly intralesional injections of Peyronie's plaques with IFN-alpha-2B resulted in a significant improvement in penile curvature, diminished pain, and reduced plaque size, and resulted in a subjective improvement in sexual function.

Adult↗

PubMedDate not supplied

Coexistence of cervicogenic headache and migraine without aura (?).

It is well known that migraine with aura may coexist with various unilateral headaches, like cluster headache and chronic paroxysmal hemicrania. It may also coexist with cervicogenic headache. The diagnosis of migraine without aura ("common migraine") poses greater problems than the diagnosis of migraine with aura. Cervicogenic headache diagnosis also poses problems when these two headaches coexist, since they have symptoms in common. Therefore, the scientific demonstration of coexistence of migraine without aura and cervicogenic headache is bound to be a difficult task. In the present study, migraine without aura and cervicogenic headache seemed to coexist in 4 patients (3 F and 1 M, mean age 50). Attacks with migraine characteristics fulfilled the IHS and IASP migraine criteria. Out of a maximum of 13 migraine characteristics based on the IHS/IASP migraine criteria, such as unilaterality, aggravation on minor physical activity, etc., none of the patients presented less than 11, as opposed to a mean of < or = 4 of these criteria in the cervicogenic type attacks. A similar system, based on criteria such as: reduction of range of motion in the neck, mechanical precipitation of attacks, etc., was also developed for cervicogenic headache. The mean number of cervicogenic headache criteria was 4.3 (out of a total of 5) in the "cervicogenic part of the picture", as opposed to 1.5 (1.8 if laterality is considered, see text) in the "migraine part of the picture". Drug regimens and anaesthetic blocks also showed different results in the two different headaches in the same patient. All in all, this study seems to support a coexistence of the two headache types.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

[Markers of cardiovascular remodeling in hypertension].

UNLABELLED: Our goal was to study the relative influence of systolic blood pressure (SBP) and plasmatic markers of sympathetic and renin-aldosterone systems (RAS) activities to left atrial diameter (LAD), left ventricular posterior wall thickness (LVPWT) and pulse wave velocity (PWV), which reflect cardiovascular remodeling in hypertension. METHODS: In 227 consecutive patients with hypertension (mean age +/- SD: 53.3 years +/- 13.4, 126 men), we measured: PWV, LAD, LVPWT, mean 24-hours SBP, plasma renin activity, and plasma aldosterone and catecholamine levels. Multiples linear regression analyses were performed to test statistical associations between hemodynamic and neurohumoral factors, and cardiovascular remodeling parameters, after adjustment for age, gender and body mass index. RESULTS: LVPWT was positively correlated to SBP as well as to plasma aldosterone and meta-noradrenaline (p < 0.001). LAD and PWV were related to SBP but not to any of the biological variables. Moreover, LAD correlated to PWV independently of SBP (p < 0.05), whereas after SBP inclusion in the model, there was not significant correlation between LAD and LVPWT nor between LVPWT and PWV. CONCLUSION: In hypertension, the development of cardiac hypertrophy depends on SBP and the sympathetic and renin-aldosterone systems activities. The RAS is not involved in the PWV nor LAD modifications. Strong association between LAD and PWV suggest that left atrial enlargement, that may be considered as a marker of diastolic function, may results more from arterial stiffness than from ventricular hypertrophy.

Adult↗

PubMedDate not supplied

Money matters.

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Economics↗

PubMedDate not supplied

Money matters.

Explore the source record for details and available documents.

Economics, Nursing↗