Hypertension and diabetes significantly enhance the risk of cardiovascular disease in patients with psoriatic arthritis.

OBJECTIVES: New evidence has lightened the linkage between psoriatic arthritis (PsA) and the development of atherosclerosis and cardiovascular disease (CVD). We aimed to describe the prevalence of cardiovascular events and associated risk factors among patients with PsA. METHODS: Retrospective evaluation of medical records from consecutive PsA patients who fulfilled the CASPAR criteria for PsA attending a specialised spondyloarthritis clinic at a single referral centre. CVD was defined based on the occurrence of coronary artery disease (CAD) or cerebrovascular ischaemic disease events. RESULTS: We evaluated 158 PsA patients, 48.7% females and 51.3% males, aged 53.7±13.9 yrs. Mean PsA duration was 13.7±8.9 yrs and polyarticular subtype affected 66 (42%) patients. According to drug therapy, 85 (54%) were using NSAIDs and 21 (13%) low-dose prednisone; 32 (20%) were on anti-TNF agents, 94 (60%) metothrexate, 18 (11%) leflunomide, 13 (8%) sulfasalazine, 5 (3%) other immunossupressors and 4 (2.5%) were on chloroquine. Over half patients (87, 55%) had arterial hypertension (AH); 51 (32%) had dyslipidaemia (DLP), 38 (29%) hypertriglyceridemia and 36 (23%) diabetes mellitus (DM). Lipid profile was similar for both genders with mean total cholesterol= 186.5±38.6mg/dl, LDL=112.3±30.6 mg/dl, HDL= 47.89±14.6 and triglycerides= 127.4± 65.6 mg/dl. Of note, 14% PsA patients have had CVD, namely cerebrovascular or coronary heart disease. Sex, age, disease duration, joint involvement subtype, disease activity, CRP and lipid levels were similar among patients with and without CVD. The prevalence of AH (95% vs. 45%, p<0.001), DLP (75% vs. 27.7%, p<0.001) and DM (60% vs. 19%, p<0.001) were significantly greater in PsA patients who have had CVD compared to those without CVD, conferring an odds ratio of 21.0 for AH and of 5.4 for DM. CONCLUSIONS: The high prevalence of CVD in PsA patients is influenced by increased AH and DM. Hence early recognition and specific treatment is mandatory in order to reduce the risk for CVD, avoiding early morbidity and mortality.

ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight.

Mice harboring 1, 2, or 3 copies of the angiotensin-converting enzyme (ACE) gene were used to evaluate the quantitative role of the ACE locus on obesity. Three-copy mice fed with a high-fat diet had lower body weight and peri-epididymal adipose tissue than did 1- and 2-copy mice (P < 0.05). On regular diet, 3-copy mice had to eat more to maintain the same body weight; on a high-fat diet, they ate the same but weighed less than 1- and 2-copy mice (P < 0.05), indicating a higher metabolic rate in 3-copy mice that was not affected by ANG II AT(1) blocker treatment. A catalytically inactive form of thimet oligopeptidase (EC 3.4.24.15; EP24.15) was used to isolate ACE substrates from adipose tissue. Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) identified 162 peptide peaks; 16 peptides were present in both groups (1- and 3-copy mice fed with a high-fat diet), whereas 58 of the 72 unique peptides were found only in the 3-copy mice. Peptide size distribution was shifted to lower molecular weight in 3-copy mice. Two of the identified peptides, LVVYPWTQRY and VVYPWTQRY, which are ACE substrates, inhibited in vitro protein kinase C phosphorylation in a concentration-dependent manner. In addition, neurolysin (EC 3.4.24.16; EP24.16) activity was lower in fat tissue from 3- vs. 1-copy mice (P < 0.05). Taken together, these results provide evidence that ACE is associated with body weight and peri-epididymal fat accumulation. This response may involve the generation of oligopeptides that inhibit the activity of EP24.16 and other oligopeptidases within the adipose tissue.

A mulher coronariopata no climatério após a menopausa: implicaçöes na qualidade de vida / The post menopausal climacteric woman with coronary artery disease: implications to quality of life

OBJETIVOS: Avaliar a qualidade de vida em mulheres com doença isquêmica do coraçäo no climatério após a menopausa. MÉTODOS: O estudo incluiu 100 mulheres após a menopausa, sendo 50 portadoras de doença arterial coronária (DAC) em seguimento no Instituto do Coraçäo (InCor) HC-FMUSP e 50 que näo apresentavam doenças associadas (grupo controle) atendidas no Centro de Saúde Escola Geraldo de Paula Souza da FSP - USP. A qualidade de vida foi avaliada mediante a utilizaçäo de dois instrumentos: uma entrevista estruturada e a aplicaçäo do questionário genérico de avaliaçäo de qualidade de vida ( SF - 36 ). RESULTADOS: Os grupos eram homogêneos em relaçäo à idade da última menstruaçäo: 49 ±3,9 anos na DAC e 49,2±3 anos no grupo controle. Os grupos também eram similares quanto à escolaridade: 84 por cento possuíam primeiro grau (completo ou incompleto); estado civil: casadas 64 por cento das DAC e 45 por cento do grupo controle e viúvas 18 por cento da DAC e 24 por cento das controle. A atividade profissional fora do lar foi significativamente mais freqüente no grupo controle (52 por cento) e 14 por cento nas DAC (p=0,0001). Ambos os grupos demonstraram percepçöes semelhantes no que se refere à sexualidade. A avaliaçäo da qualidade de vida pelo SF - 36 mostrou melhores resultados no grupo controle em relaçäo a: capacidade física (84 vs 50,5 na DAC); aspectos físicos (84 vs 45,5); estado geral de saúde (87,2 vs 59,1); vitalidade (69,7 vs 51,4) e escore total dos componentes mentais (70,4 vs 58,6). CONCLUSÄO: A coronariopatia interfere na qualidade de vida das mulheres após a menopausa, limitando a capacidade física e o desempenho das atividades da vida diária, além de intensificar as dificuldades emocionais desse período

[The post menopausal climacteric woman with coronary artery disease: implications to quality of life]. / A mulher coronariopata no climatério após a menopausa: implicações na qualidade de vida.

PURPOSE: To analyse the quality of life of post menopausal women with coronary artery disease. METHODS: The population consisted of 100 women, divided into 2 groups. The first group made up of 50 women whose average age was 58 +/- 4,2 years with > stable coronary artery disease (CAD) proved by angiography undergoing treatment at The Heart Institute (InCor) - University of São Paulo Medical School, Brazil (CAD group). This group was compared with 50 women (55.1 +/- 5.4 years old) without clinical evidence of coronary artery disease (control group) from a primary health care center, Centro de Saúde Escola Geraldo de Paula Souza, São Paulo - FSP- USP. The quality of life was assessed by a structured interview and by Medical outcomes study 36-item short-form health survey (SF-36) validated to the Brazilian population. RESULTS: They were homogenous regarding age of the last menstruation period: 49 +/- 3.9 years old in CAD and 49.2 +/- 3 years old in controls. The groups were also similar in education level, marital status (64% of CAD and 45% of controls were married; and 18% of CAD and 24% of controls were widowhood). The active working status was more frequent in controls than in CAD (52% vs. 14%; p= 0.0001). Both groups showed similar perceptions in their sexual experience. The evaluation of quality of life by SF-36 showed better scores for the control group in: physical functioning (84 vs. 50.5), role physical (84 vs. 45,5), general health (87.2 vs. 59.1), vitality (69.7 vs. 51,4), p<0.0001; and total score of mental components (70.4 vs. 58.6), p = 0.028. CONCLUSION: Coronary artery disease alters the quality of life of climacteric women by limiting the physical capacity to perform ordinary daily activities and by intensifying emotional conflicts usually present in this phase of life.

Rabbit spinal cord infarctuated upon aluminum (III)-liposomes intravenous treatment.

The present paper describes toxic effects of liposomes containing aluminum lactate (AlLac3) (Al-liposomes) on rabbits spinal cord after intravenous treatment of 42 days with 60 micrograms per day of metal-ion as AlLac3 at neutral pH as compared with an aqueous solution of the same metastable Al compound. Among the tissues examined, spinal cord appear to be the most injured one with large infarctual zones where Al is accumulated. Differently, the aqueous solution of AlLac3 is ineffective. Toxic aspects of Al lipophilic forms are herein discussed in terms of pharmacological implications.

Clinical application of genetic polymorphism in neurofibromatosis type 1.

The authors report the study of DNA polymorphic sequences, 5 intragenic and 5 flanking the NF1 gene, in 87 Italian NF1 families for a total of 142 affected individuals and 204 non-affected relatives. All PCR-based analyses are easy and simple to perform, and require small amounts of DNA. The non radioactive method used is sensitive, rapid, and has low background. All subjects were informative for at least 2 markers. The use of linkage study to familial cases allowed us to exclude the diagnosis prenatally in two fetuses, and to confirm or exclude diagnosis in those relatives with clinical signs, but not fulfilling the international diagnostic criteria. Furthermore indirect analysis permitted the detection of large gene deletions by loss of heterozygosity of one or more DNA markers in three out of 47 sporadic cases.

[Heart surgery in childhood. Impact on the quality of life of adolescents]. / Cirurgia cardíaca na infância. Repercussões na qualidade de vida do adolescente.

PURPOSE: To assess quality of life in patients submitted to surgical treatment of congenital heart disease in infancy. Quality of life has been assessed over social sciences backgrounds, but we have focused on the patient self-perception of their disease and related problems too. METHODS: We studied 134 adolescents, age ranged from 12 to 19 year-old, of both sexes, with any congenital heart disease, submitted to surgical treatment in infancy. They answered a questionnaire that covered their clinical, social, emotional, education and professional status. RESULTS: Ninety one percent qualified their lives as good because were symptom-free and living well without and physical restriction. CONCLUSION: The school performance was similar to the overall population engaged in Brazilian public schools. Their feelings, social relations and future plans were equal to the normal adolescents.

Deposition of aluminum in brain tissues of rats exposed to inhalation of aluminum acetylacetonate.

The present paper reports data concerning aluminum accumulation and compartmentation in the central nervous system from rats exposed by inhalation to aluminum acetylacetonate [Al(acac)3] for two weeks. The complex Al(aca)3 was chosen for being neutral, hydrolytically stable and lipophilic. After animals treatment, Al(III) was identified fluorimetrically by using morin (3,5,7',2',4'-pentahydroxyflavone) that gives a specific green-yellow fluorescence when complexed to the metal. Al(III) was observed to be accumulated in the brain cortex, hippocampus, enthorinal area, olfactory bulb as well as in the Purkinje cells of cerebellum, and in the white matter.

The inhibition of trypsin and alpha-chymotrypsin proteolytic activity by aluminum(III).

In Alzheimer's disease, among different hypotheses, amyloid is thought to be formed from a disequilibrium between proteases and protease inhibitors with a consequent production of self-aggregating fragments that are deposited in brain tissues. In this paper we present evidences that aluminum(III) can be a candidate for playing a dismetabolic role in inhibiting the proteolytic activity of the serine proteases trypsin and alpha-chymotrypsin, and the inhibitory reaction can be reversible in the presence of EDTA. The relevance of the physicochemical properties of the metal coordination sphere in this inhibitory effect is also discussed.

Differential aluminium lactate toxicity in rabbits using either aqueous solutions or liposomal suspensions.

The present paper deals with the toxic effects of aluminum lactate (Al(lact)3) in rabbits. Experimental animals were injected with 6.2 mg of Al(III) as Al(lact)3 aqueous solutions at neutral pH for 21 days. Histological examination showed different pathological lesions to the myocardial tissue, spleen, kidney and liver, with no relevant effects to lungs and CNS. On the contrary, rabbits injected with 60 micrograms of Al(III) as Al(lact)3 in a liposome suspension for 42 days showed a large infarctual zone in the spinal cord with the metal accumulation in the necrobiotic neurons. Pharmacological implications of these findings are also discussed.

Evaluation of heavy metal pollution in the Venetian lagoon by using Mytilus galloprovincialis as biological indicator.

This study reports the analysis of heavy metal (Cd, Co, Cu, Cr, Hg, Fe, Mn, Ni, Pb, Zn) and As accumulated in the mollusc Mytilus galloprovincialis collected in the Venetian lagoon between March and September 1988. This environmental biomonitoring project was carried out using natural population of the molluscs attached to the 'Briccole', which limit the navigation canals into the lagoon. These data were compared with those reported by other authors in analogous studies published about a decade ago. A small improvement on the heavy metal pollution of the Venetian lagoon can be deduced from this comparison, presumably depicting a positive signal of a new downward trend in metal concentrations. Continuous monitoring of the fragile lagoonal ecosystem must be an important commitment due to the economic and historical importance of the Venetian lagoon.

Resolution of serum aluminum-binding proteins by size-exclusion chromatography: identification of a new carrier of aluminum in human serum.

We have examined the use of TSK-GEL HW 55S for determining the distribution of aluminum in human serum by size-exclusion chromatography (SEC). In comparison to other SEC matrices, this material has less affinity for ionized aluminum and separates serum proteins and their aluminum complexes with greater resolution. This enabled the identification of a previously unknown protein carrier, provisionally called albindin, that binds aluminum with great stability. Albindin appears to be distinct from the previously described aluminum carriers albumin and transferrin and may be important in the pathogenesis of disease secondary to hyperaluminemia.

Aluminum-binding serum proteins: desferrioxamine alters serum aluminum speciation.

The aluminum content of four size classes of protein (high and low molecular weight, transferrin/albumin and a fraction provisionally termed albindin) in sera from healthy volunteers (group I) and from aluminum workers with normal (group II) and high (group III) total serum aluminum was compared using size exclusion chromatography and electrothermal atomic absorption spectroscopy. In the absence of any drug treatment the transferrin/albumin fraction was the major carrier, containing 29% to 33% of the aluminum recovered, in all three subject groups. Desferrioxamine treatment of groups II and III significantly decreased the proportion of aluminum bound by albumin/transferrin (P less than 0.05 in group III) and increased that bound by albindin (P less than 0.05 in groups II and III). The albindin fraction contained over 40% of the aluminum recovered from sera of group III subjects during desferrioxamine treatment. We conclude that the albindin fraction contains a protein or proteins that can form stable complexes with aluminum which may be important in preventing aluminum toxicity.

Effects of aluminum speciation on murine neuroblastoma cells.

Murine neuroblastoma cells behave differently in the presence of Al(acac)3 [acac = 2,4-pentanedionate; acetylacetonate] or Al(malt)3 [malt = 3-hydroxy, 2-methyl, 4-pyronate; maltolate] with respect to Al(lac)3 [lac = 2-hydroxypropionate; lactate]. Thus, a remarkable cytotoxic effect was observed in the first case; on the contrary, an evident cytostatic and neuritogenic effect was produced by aqueous Al(lac)3. The hydrolytically stable complexes Al(acac)3 and Al(malt)3 were both toxic in the concentration range of 0.10-0.30 and 0.10-0.50 mM, respectively, over 24 h. In contrast with this behavior Al(lac)3 displayed a potent cytostatic activity with induction of neurites at 0.2-10 mM. Al(OH)3 manifested biological effects comparable to those exhibited by Al(lac)3. AlPO4 was also cytostatic and led to a morphological differentiation of the neuroblastoma cells, qualitatively different from that elicited by Al(lac)3. The morphological effects induced by Al(lac)3, Al(OH)3, and AlPO4 were irreversible.

Aluminum(III) influences the permeability of the blood-brain barrier to [14C]sucrose in rats.

To determine the influence of the metal coordination sphere on the permeability of the blood-brain barrier (BBB), rats were injected intraperitoneally with aluminum lactate (Al(lact)3), aluminum acetylacetonate (Al(acac)3), aluminum maltolate (Al(malt)3) at pH 7.5, or with physiological saline. Two h after each treatment, [14C]sucrose physiological saline solution was injected in animals, and the radioactivity was measured in 5 brain regions (cerebral cortex, mesencephalon, diencephalon, medulla-pons, cerebellum). Radioactivity was significantly elevated in brains from animals treated with Al(malt)3 (hydrolytically stable and hydrophilic), and with Al(acac)3 (hydrolytically stable and lipophilic) but not with Al(lact)3. Time-course study carried out at 2, 4 and 24 h with different aluminum compounds showed a persistent radioactivity 24 h after treatment only in the brain from animals treated with Al(acac)3. Morin stain localized AlIII only in neurons from animals treated with Al(acac)3. These findings indicate that AlIII alters the BBB function in the rat either permanently or transiently depending on the physiochemical properties of the metal coordination sphere. Implications of these results, in terms of AlIII as a potential toxic factor in humans, are considered and discussed.

A long-term toxicological investigation on the effect of tris(maltolate)aluminum(III) in rabbits.

The toxicity of i.v. injected hydrophilic aluminum complex tris(maltolate)aluminum(III) was studied in New Zealand white rabbits for a period of time ranging from 5 to 63 wk. Animals were injected 3-5 times a week with 1 mL of 7.5 mM Al(malt)3 and one rabbit with a dose 10 times higher after 14 wk of treatment. Autopical examination was performed on all animals. Chemoclinical analysis (glucose, urea, creatinine, cholesterol, bilirubin, alanin aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, LDH, CK, total protein, triglycerides, and Ca2+) gave no variation in treated animals with respect to the control. The toxicological data show a moderate systemic general toxicity at doses far higher than those used in similar previous experiments using Al(acac)3 (acac = 2,4 pentanedionate), a hydrolytically stable and more lipophilic aluminum(III) complex (1). The diversity of behavior is discussed in terms of metal speciation as well as respect to the thermodynamic and kinetic properties of the two complexes in aqueous solution. The toxicological model presented here emphasizes that neutral, water compatible aluminum(III) complexes are to be considered as promising tools for toxicological experiments providing biological models of human pathologies.

Experimental aluminum pathology in rabbits: effects of hydrophilic and lipophilic compounds.

Aluminum lactate [Al(lact)3] (hydrophilic, hydrolytically unstable) and aluminum acetylacetonate [Al(acae)3] (lipophilic, hydrolytically stable) were tested as potential toxicants to rabbits upon IV administration both as aqueous solutions and as liposome suspensions. Both chemicals behaved as cardiotoxic agents when administered as aqueous solutions, but Al(acae)3 was at least two orders of magnitude more active than Al(lact)3. Al(acae)3, but not Al(lact)3, caused myocardial infarcts resembling those in humans (with contraction bands) at doses as low as 0.24 mg/kg body weight, as well as a prominent acanthocytosis. Al(lact)3, when administered as a liposome suspension, was about 300 times more toxic than in aqueous solution, although cardiac damage was not infarctual in character. Both chemical and physical speciation of aluminum(III) thus play an essential role in determining the toxicity of the metal.