Coronary calcification in hemodialysis patients: the contribution of traditional and uremia-related risk factors

BACKGROUND: Coronary artery calcification is a common feature of atherosclerosis, occurring in 90% of angiographically significant lesions. There is recent evidence that coronary artery calcification is frequent in hemodialysis patients and it has been suggested that this increased incidence may be associated to uremia-related factors. The development and progression of coronary artery calcification is similar to osteogenesis. The aim of this study was to evaluate the relationship between coronary artery calcification, uremia-related factors, and bone histomorphometry in hemodialysis patients. METHODS: A total of 101 hemodialysis patients were assessed for biochemical markers of inflammation, oxidative stress, and bone metabolism. Subsequently, they were submitted to multislice coronary tomography (MSCT) and transiliac bone biopsy. RESULTS: The median calcium score was 116.2 (range 0 to 5547). Fifty-two percent of the patients showed moderate and severe coronary artery calcification, 20% had calcium scores greater than 1000. In univariate analysis, age (r= 0.57, P < 0.000001), osteoprotegerin (OPG) (r= 0.44, P= 0.00002), and body mass index (BMI) (r= 0.24, P= 0.01) correlated positively with calcium score. Bone trabecular volume and trabecular thickness correlated negatively with calcium score (r=-0.24, P= 0.02; r=-0.22, P= 0.03). There was a correlation of borderline significance between calcium score and C-reactive protein (CRP) (r= 0.18, P= 0.062). The multiple linear regression analysis identified OPG as the only variable independently associated with coronary artery calcification. CONCLUSION: Coronary artery calcification is highly prevalent in the hemodialysis population and is associated with older age, higher BMI, inflammation and reduced trabecular bone volume. Higher OPG is independently associated with coronary artery calcification and may represent an incomplete self-defensive response to the progression of atherosclerosis in hemodialysis patients.     

Drug and multidrug resistance among Mycobacterium leprae isolates from Brazilian relapsed leprosy patients

Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary.     

Turner syndrome: searching for better outcomes

OBJECTIVES: To assess the results of growth hormone on the growth of girls with Turner Syndrome and identify relevant parameters to improve outcomes. METHODS: Growth velocity and final height were studied in a historical cohort of 41 girls, regularly followed up for hormone distribution at three referral centers. The influence of oxandrolone and of estrogens on the final height was analyzed. The girls (initial chronological age=8.9+/-3.4years; initial bone age=7.0+/-3.1years) used 0.19 mg/kg/week of growth hormone for 4.0 +/- 2.0 years. RESULTS: In the first year, growth velocity increased by 71.5% in 41 girls and 103.4% in those who reached final height (11 girls). The whole group had a gain in the height SDS of 0.8 +/- 0.7 (p<0.01) and for those who reached a final height of 1.0 +/- 0.8 (p<0.01). Final height (143.6 +/-6.3 cm) was 3.9 +/- 5.3 cm higher than the predicted height, and the height gain occurred before estrogen therapy. Oxandrolone had no significant influence on height gain. The significant variables contributing to the final height were the duration of growth hormone used and its use prior to starting estrogens, the initial height SDS, and the growth velocity during the first year of treatment. CONCLUSIONS: We concluded that the use of growth hormone significantly increased the final height, which remained lower than the target. Results point to a need for starting growth hormone use as early as possible and to maximize treatment before estrogen replacement. It has been observed that even moderate doses of growth hormone may significantly increase early growth velocity.     

Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.

OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain symptoms of hypersensitivity. METHODS: Between January 1985 and January 2007, all adverse drug reactions (ADRs) reported to the Netherlands Pharmacovigilance Centre Lareb related to AEDs as suspected drugs were included in this study. ADRs were analysed using a case/non-case design. Cases were defined as those patients with ADRs involving symptoms of hypersensitivity. Non-cases were patients with all other ADR reports. Symptoms of hypersensitivity were classified according to the Gell and Coombs classification (type I-IV) and the organ involved (e.g. cutaneous, hepatic). AEDs were classified as aromatic anticonvulsant if their chemical structure contained at least one aromatic ring. All other AEDs were classified as non-aromatic. We assessed the strength of the association between aromatic AEDs versus non-aromatic AEDs and reported hypersensitivity reactions with logistic regression analysis and expressed these as reporting odds ratios (RORs). RESULTS: In total, 303 cases of hypersensitivity associated with the use of AEDs were reported. Aromatic AEDs were suspected in 64.4% of these reports versus 41.3% (574/1389) of the non-hypersensitivity reports. A significant ROR of 2.15 (95% CI 1.63, 2.82) was found for aromatic AEDs and all hypersensitivity reactions. Aromatic AEDs were significantly associated with immunoglobin E-mediated type I hypersensitivity reactions (ROR 2.15; 95% CI 1.23, 3.78) and T-cell-mediated type IV reactions (ROR 6.06; 95% CI 3.41, 10.75). Type II and III reactions did not show an association. Cutaneous symptoms represented 39.9% of the hypersensitivity-related ADRs. Aromatic AEDs were significantly associated with cutaneous hypersensitivity reactions (ROR 5.81; 95% CI 3.38, 9.99). CONCLUSION: This study confirms that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains apparent 'idiosyncratic' hypersensitivity reactions. Symptoms of hypersensitivity were reported twice as frequently with aromatic AEDs than with non-aromatic AEDs. Strong associations for aromatic AEDs versus non-aromatic AEDs were found for T-cell-mediated (type IV) reactions, as well as for cutaneous reactions.     

Differential activation of protein kinase C isoforms by euxanthone,revealed by an in vivo yeast phenotypic assay

The protein kinase C (PKC) modulatory effects of euxanthone, isolated from the wood of Cratoxylum maingayi, on isoforms alpha, betaI, delta, eta and zeta were characterised using an alternative in vivo yeast phenotypic assay. The present study shows that euxanthone can activate isoforms alpha, betaI, delta, eta and zeta, being more effective on PKC-betaI, -delta, -eta and -zeta than the established PKC activators used (the phorbol ester PMA and arachidonic acid for PKC-zeta). Furthermore, euxanthone presents differences on its potency towards individual PKC isoforms, showing a remarkable selectivity for PKC-zeta. These results can help to clarify the molecular basis of the euxanthone-mediated effects.     

Determination of capsaicinoids in topical cream by liquid-liquid extraction and liquid chromatography

A reversed-phase liquid chromatography (LC) method has been developed, optimised and validated for the separation and quantitation of capsaicin (CP) and dihydrocapsaicin (DHCP) in a topical cream formulation. Sample preparation involves liquid-liquid extraction prior to LC analysis. The method uses a Hypersil C(18) BDS, 5 micrometer, 250x4.6 mm I.D. column maintained at 35 degrees C. The mobile phase comprises methanol, water, acetonitrile (ACN) and acetic acid (47:42:10:1, v/v/v/v) at a flow rate of 1.0 ml/min. Robustness was evaluated by performing a central composite face-centred design (CCF) experiment. The method shows good selectivity, linearity, sensitivity and repeatability. The conditions allow the separation and quantitation of CP and DHCP without interference from the other substances contained in the cream.     

Investigation of deaths in an area of groundnut plantations in Casamance,South of Senegal after exposure to Carbofuran,Thiram and Benomyl

Between May and October 2000, the Regional Health Office of Kolda Region in the south of Senegal, West Africa, reported an epidemic of an unknown illness characterized by thoracic pain, dyspnea and edemas of limb and face. The epidemic covered a radius of approximately 40 km (24 miles) between the districts of Kolda and Sedhiou in Kolda Region. Cases were mostly men whose age ranged between 12 and 60 years old. Investigation revealed that they had been exposed to pesticides distributed by the government to groundnut farmers. The signs and symptoms suggested intoxication with carbamates, carbofurans, and possibly thiram, contained in the pesticides distributed with the groundnut seeds. Government distribution created an excessive use of pesticides in the farms, and consequently an overexposure of the subjects who handled the seeders, especially young males but also a small proportion of women who worked in the groundnut fields. Many of these subjects, not accustomed to handle pesticides, came to overestimate the quantity of product to fill the seeder. It should be noted that the policy of distribution of pesticides in Senegal, which presents risk of poisoning, was not systematically accompanied by sufficient information on the danger of the products and of certain precautions that should be taken during their use.     

Analgesia and c-Fos expression in the periaqueductal gray induced by electroacupuncture at the Zusanli point in rats

The need to use anaesthetised or restrained animals in acupuncture research in laboratory animals may represent a confounding variable, since both anaesthesia and stress alter the pain threshold and the activity of pain-related brain areas. In the current study we assessed the participation of the periaqueductal gray (PAG) in electroacupuncture's (EA) analgesic effects applied to the Zusanli point (36S) under carefully controlled stress conditions. Repeated immobilisation protocols (6 days, 1 h/day and 13 days, 2 h/day) were used to diminish the influence of acute immobilisation stress on c-Fos expression and analgesia (tail-flick test) induced by electroacupuncture on the 36S point (EA36S). Animals submitted to immobilisation alone (IMMO) or to electroacupuncture (100 Hz, 2-4 V, faradic wave) on a non-point region (EANP) were compared with animals submitted to electroacupuncture on the 36S point. In animals not previously submitted to repeated immobilisation, electroacupuncture on the 36S point induced analgesia and c-Fos expression in the PAG was not different from that induced by electroacupuncture at a non-acupuncture point. In animals submitted to repeated immobilisation (repeated immobilisation for 6 days or repeated immobilisation for 13 days), however, electroacupuncture on point 36S led to higher levels of analgesia and c-Fos expression, specifically in the ventrolateral PAG (vlPAG), as compared with animal groups subjected only to immobilisation or to electroacupuncture on a non-point. Our findings endorse previous results, and point to a specific part of the PAG involved in the effects of electroacupuncture at the Zusanli point.