Complement and contact system activation in acute congestive heart failure patients.

Recent experimental data indicate a pathogenic role of complement activation in congestive heart failure (CHF). The aim of this study was to evaluate contact and complement systems activation in patients hospitalized for an acute episode of CHF. Forty-two of 80 consecutive patients admitted at our hospital with confirmed diagnosis of acute CHF were enrolled. They underwent blood sampling within 24 h from admission (T0) and at clinical stability (T1). Patients were stratified for ejection fraction (EF) based on echocardiographic test. We measured plasma levels of C3, C4, sC5b-9 and cleaved high molecular weight kininogen (contact activation marker). At T1, C3 levels increased significantly compared to T0 (97 ± 2 versus 104 ± 3% of total pooled plasma, P < 0·01). Classifying patients according to EF, only patients with preserved EF presented a significant increase of C3 from T0 to T1 (99 ± 3 versus 108 ± 4%, P = 0·03). When the sample was stratified according to clinical outcome, C3 (98 ± 3 versus 104 ± 4%, P = 0·03) and sC5b-9 levels (204 ± 10 versus 230 ± 11 ng/ml, P = 0·03) were increased in patients who had positive outcome after hospitalization. CHF patients with preserved EF and positive outcome after hospitalization showed higher levels of sC5b-9 in the T1 period compared with T0 (211 ± 14 versus 243 ± 14 ng/ml, P = 0·04). Our results suggest that the complement system reacts differently if CHF occurs with preserved or reduced EF. This finding is interesting if we consider the difference in epidemiology, pathogenesis and possible therapeutic approaches of these two clinical entities.

Association between the presence of protein bands in ram seminal plasma and sperm tolerance to freezing.

This study evaluated associations between the presence of protein bands in ram seminal plasma and the quality of sperm frozen with distinct extenders. Ejaculates were frozen in a Tris-egg yolk based extender, including either 5% glycerol or 100mM trehalose. Seminal plasma samples were submitted to unidimensional electrophoresis. Pre-freezing and post-thawing sperm quality was similar between extenders (P>0.05). A total of 26 bands were identified in ram seminal plasma. Pre-freezing sperm motility was increased when the 15, 19 and 80kDa bands were present in seminal plasma (P<0.05). The presence of an 11kDa band in seminal plasma was associated with reduced pre-freezing membrane integrity (P<0.05). After thawing, both sperm motility and membrane integrity were reduced when a 24kDa band was present in seminal plasma (P<0.05). Post-thawing acrosome integrity was greater in the presence of a 31kDa band in seminal plasma (P<0.05). Regardless of the cryoprotectant included in the freezing extender, these six bands may be potential markers for ram sperm tolerance to freezing.

Equine-derived bone substitutes in orthopedics and traumatology: authors' experience.

AIM: To evaluate the use of equine-derived bone grafts in the treatment of bone loss in a heterogeneous clinical case series. METHODS: The study population was 48 patients (29 males and 19 females; mean age, 49 years; range, 9-84); the orthopedic defect site was located on the right side in 22 and on the left side in 26 cases. The graft material was antigen-free equine-derived collagen bone cleaned with an enzymatic treatment. RESULTS: Clinical and radiographic healing times were virtually similar; graft osseointegration needed from two to three months longer to heal. CONCLUSION: The outcome after grafting with an equine-derived bone substitute was satisfactory. Further study is needed to demonstrate its statistically significant effectiveness in the treatment of orthopedic defects like those in this series.

From pilot to mainstream: a decade of working in partnerships to expand access to emergency contraception in Mexico.

Emergency contraception (EC) is used post-coitally and offers women an important second chance to prevent pregnancy. Approximately 10 years ago, Mexico became one of the earliest countries working to expand EC access. Partners came together to pursue a synergistic four-pronged strategy, including product registration, health care provider training and orientation, awareness raising among the general public, and policy change. By 2006, five EC products were registered and sold in Mexico, EC was widely available through pharmacies and included in the public sector contraceptive options, and knowledge of the method had increased substantially.

Treatment of incomplete abortion and miscarriage with misoprostol.

A literature review was conducted to determine whether misoprostol is an effective treatment for incomplete abortion and, if so, to recommend an appropriate regimen. All English language articles published before October 2007 using misoprostol in at least one of the study arms were reviewed to determine the efficacy of misoprostol when used to treat incomplete abortion in the first trimester. All available unpublished data previously presented at international scientific meetings were also reviewed. Sufficient evidence was found in support of misoprostol as a safe and effective means of non-surgical uterine evacuation. A single dose of misoprostol 600 microg oral is recommended for treatment of incomplete abortion in women presenting with a uterine size equivalent to 12 weeks gestation.

PON1 activity and genotype in patients with arterial ischemic stroke and in healthy individuals.

OBJECTIVE: Paraoxonase-1 (PON1) is an esterase with antioxidant properties. Low PON1 enzyme activity or specific allelic polymorphisms seem to be associated with the risk of developing coronary artery disease or acute ischemic stroke (AIS). Our objective was to determine the distribution of both PON1 enzyme activity and its genotype in a group of patients with AIS. MATERIALS AND METHODS: PON1 activity and the relative Q192R and L55M polymorphisms in the PON1 gene were assessed on 126 survivors of a first AIS and in 92 healthy subjects. RESULTS: The genotype distribution for PON1 Q192R and L55M polymorphisms was similar in AIS patients and healthy subjects, but patients carrying the QRLL or RRLL genotype combination had lower PON1 enzyme activity compared with healthy subjects with the same genotype. CONCLUSION: We postulate that lower than expected PON1 enzyme activity within specific genotypes might explain the reported association between R and L alleles and the risk of developing AIS.

Hyperferritinaemia without iron overload: pathogenic and therapeutic implications.

It is not unusual to meet increased levels of ferritinaemia in patients apparently healthy. Among other causes of hyperferritinaemia, recently was described the Hereditary Hyperferritinemia Cataract Syndrome, a genetic condition characterized by increased serum ferritin values without iron overload and bilateral nuclear cataract, both of early onset. It has been demonstrated that single or double point mutations or deletions in the stem-loop structure of the iron regulatory element (I.R.E.) located in the 5 untranslated regions of the ferritin L-subunit gene (19q13.1) are responsible for the upregulation of ferritin. This overexpression only for the L-chain gives rise to typical piles in several tissues. When this altered ferritin accumulates in lens it causes bilateral nuclear cataracts, that is the peculiar sign of this syndrome. It is essential to differentiate true iron overload from Hereditary Hyperferritinaemia Cataract Syndrome (H.H.C.S.), because these patients rapidly develop iron deficient anaemia when venosectioned. Here we describe a case report about a 40 years old healthy female blood donor who presented isolated hyperferritinaemia without iron overload, in the absence of concomitant pathologies. Anamnestic, biochemical, instrumental and clinical investigations led us to diagnose H.H.C.S., a pathology first described in 1995. From 1995 to date about 40 cases concerning patients showing the characteristics of this syndrome from Europe, USA, and Australia were described. Biochemical, genetical and clinical investigations led finally to understand every matter of this pathology, providing conclusive and exhaustive explanations.

On the mechanisms of action of short-term levonorgestrel administration in emergency contraception.

The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri- and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.

Do different dialytic techniques have different atherosclerotic and antioxidant activities?

To compare the chronic effect of several dialytic techniques (bicarbonate dialysis, BHD; acetate free biofiltration, AFB; hemodiafiltration, HDF; paired filtration dialysis, PFD) on atherosclerosis and antioxidant activity, three different indices were created. The first (atherosclerotic index = AI) is formed using the sum of three plasma substances: MDA, Hcy, and Cys (malondialdehyde, homocysteine, cysteine). The second (antioxidant activity index = AOAI) is the sum of five erythrocyte (E) parameters: E-GSH, GPx, CAT, SOD, GR (E-glutathione, E-glutathione peroxidase, E-catalase, E-superoxide dismutase, E-glutathione reductase). The third (defense index = DI) is derived from the previous two: (AOAI - AI). The indices were so expressed as AI in mmol/L, AOAI in U/g hemoglobin (Hb), and DI in arbitrary units. These indices were calculated in 20 controls and 51 chronic HD patients (26 female, 25 male) before, during, and after the first session of the week. HD patients were divided according to their dialytic technique: BHD, n = 35; AFB, n = 5 patients; HDF, n = 7 patients; or PFD = 4 patients. All patients had been treated with a given technique for at least 12 months, before entering the study. As expected, HD patients had AI values higher than controls, both before and after the session, with a mean value of 541 (before) and 331 (after), whereas controls had a mean value of 205. The AOAI was lower than controls, both before and after the session, the mean value being 1,122 (before) and 1,582 (after), that of controls being 2,424. In all cases, PFD gave the best "acute" results; at the end of a PFD session, near normal values of AI, AOAI, and DI (defensive index = AOAI - AI) were obtained.

Polymorphisms of the apolipoprotein E gene regulatory region and of the LDL receptor gene in late-onset Alzheimer's disease in relation to the plasma lipidic pattern.

Two new polymorphisms in the regulatory region of the apolipoprotein E gene, -491 A/T and -427 T/C, have been reported to be associated with the risk of Alzheimer's disease (AD). Moreover, in vitro studies suggest that the two polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the MspI polymorphism in the LDL receptor gene, in a series of elderly patients with late-onset sporadic AD and in an age-matched control group but failed to find any kind of association between these genetic features and an increased risk of AD. In the same samples we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymorphism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE levels. The -427 TT homozygotes had lower, and the -491 AA homozygotes had higher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of -491 A/T and -427 T/C polymorphisms on APOE promoter transcription activity.

Role of cellulosic and noncellulosic membranes in hyperhomocysteinemia and oxidative stress.

Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease (ESRD) with an increased relative risk (RR) of 1% per micromol/L in total homocysteine concentration. In ESRD patients who undergo hemodialysis (HD), the antioxidant system is largely inadequate in correcting the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of several cellulosic (CMs) and noncellulosic of synthetic membranes (NCMs) upon hyperhomocysteinemia and the oxidative stress, we measured plasma (P) homocysteine (t-HCY), plasma lipid peroxidation (LPO), and erythrocyte (E) concentration of several antioxidant enzymes in 20 normal subjects, in 35 HD patients treated with CMs, and in 29 patients treated with NCMs. Before, during, and after the first session of the week (at times 0', 120', end, 30' after HD end), blood samples were drawn. Plasma (P) homocysteine (t-HCY), cysteine (CYS), malondialdehyde (MDA), erythrocyte (E)-glutathione (GSH), glucose-6-phosphodehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide-dismutase (SOD) were determined. The dialytic procedure significantly decreased the three plasma parameters, but none normalized (as a mean). The E-enzymes scavenging ROS (lower than normal before session) increased throughout the session, but the normal range of activity was never reached. Different membranes have shown different effects. When these effects on P and E spaces were pooled, we were able to classify the membranes as follows. In a general sense, cellulosic membranes are less effective than synthetic membranes both on lipoperoxides (LPO) and antioxidant activity (AOA). Among synthetic membranes, PMMA is the best membrane both for plasma values and lesser enzymatic derangement during the session. A practical system for classifying the anti-atherosclerotic action and antioxidant activity of dialytic membranes is proposed.

Homocysteine as a cardiovascular risk factor.

UNLABELLED: Hyperhomocysteinemia (HH), a known risk factor for vascular diseases, is a frequent condition in hemodialysis (HD) patients. HH induces an oxidant stress to the vascular endothelium, causing a failure of vasodilation and an impairment of the antithrombotic properties. Vitamins B(6), B(12) and folic acid are important cofactors for the enzymes in the catabolism of homocysteine (Hcy). Failure of Hcy catabolism forces the cell to export Hcy into the plasma. The kidney is an important metabolic site for removal (up to 70%) of plasma Hcy (P-Hcy). HD lowers the P-Hcy concentration by 29 and 41% with cellulosic and noncellulosic membranes, respectively, yet values return to normal in only a few patients. Clearly, we must decrease the dangerous high levels of Hcy in different ways. Vitamin Supplementation: Vitamins B(6), B(12) and folic acid decreased the basal level of Hcy by about 40%, starting from the sixth month. Membranes: Some membranes performed better than the others. TECHNIQUES: On the chronic basis, in our 1-year experience, paired filtration dialyis led to the best results, when compared to bicarbonate dialysis and acetate-free biofiltration. Finally, as in HD patients no one type of treatment can normalize the P-Hcy concentration, we should try other, different strategies such as absorption, the use of liposomes and new types of supplementation.

[Emergency contraception: a simple, safe, effective and economical method for preventing undesired pregnancy]. / Anticoncepción de emergencia: un método simple, seguro, efectivo y económico para prevenir embarazos no deseados.

In the following article, the most recent knowledge on emergency contraception (EC) is reviewed. EC is defined as those contraceptive methods that may be used to prevent an unwanted pregnancy up to 3 days after unprotected intercourse, contraceptive failure or rape. In case of non-hormonal methods (IUD), the time window for pregnancy prevention goes up to 5 days after intercourse. The different regimens now available, hormonal and non-hormonal methods, indications, contraceptive effectiveness, side effects and safety profile, possible mechanisms of action and counseling strategies will be reviewed. The potential benefits on reproductive health of wide-spread knowledge and easy, non-restrictive access to this methodology are emphasized. An extensive list of recent references is enclosed.

An overview of haemodialysis and oxidant stress.

Today's patient population is increasingly older. Patients with chronic renal failure therefore start extracorporeal substitutive treatment having congestive heart failure, chronic liver disease, diabetes and so forth. In these patients, however, long-term haemodialytic treatment may add further aggravation on their pre-existing pathological conditions. Oxidative stress and alterations in lipid metabolism are caused by haemodialysis mainly due to (1) bioincompatibility type of reactions such as production of reactive oxygen species by inflammatory cells due to complement-mediated or -independent pathways, and (2) the imbalance between oxidants and antioxidants due to the diffusive loss of hydrophilic vitamins such as ascorbic acid. The events related to the oxidant stress may sustain a state of chronic inflammation. Recent advances suggest that atherosclerosis and proliferation of the smooth muscle are initiated and sustained by inflammatory mechanisms. Therefore, attempts to counterbalance the prooxidant effect of haemodialysis and to reduce the chronic inflammatory state will be presented.

Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease.

Besides apolipoprotein E (APOE) polymorphism, whose association with Alzheimer's disease (AD) has been confirmed in most of the numerous population samples studied, other markers have been investigated. In most cases the association firstly described was not confirmed in subsequent works. Since it is important to examine these associations in as many populations as possible, we investigated APOE, APOC1, APOC2, alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) polymorphisms in a series of elderly patients with late-onset sporadic AD from Northern Italy and in a sex and age-matched control group. We could not confirm the significantly higher frequency of the ACT*A allele among carriers of APOE e*4 allele described elsewhere, although a similar trend was observed. The APOC2 and the PS-1 distributions were similar between patients and controls. However, we observed a significant difference in the genotype and allele frequencies of APOE and APOC1: patients had higher e*4 and C1*2 allele frequencies. This finding confirms the important role for APOE in AD occurrence. In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk. In contrast to previously reported data, plasma apoE concentrations were similar in patients and in controls. An interaction between APOE and APOC1 polymorphisms and apoE levels was observed in patients: subjects carrying the APOE E3/E2 or the APOC1 2-2 genotype have higher apoE concentrations than those who do not.

Emergency contraception in Mexico City: what do health care providers and potential users know and think about it?

Emergency contraception promises to reduce Mexico's high unwanted pregnancy and unsafe abortion rates. Because oral contraceptives are sold over-the-counter, several emergency contraceptive regimens are already potentially available to those women who know about the method. Soon, specially packaged emergency contraceptives may also arrive in Mexico. To initiate campaigns promoting emergency contraception, we interviewed health care providers and clients at health clinics in Mexico City, ascertaining knowledge, attitudes, and practices concerning the method. We found limited knowledge, but nevertheless cautious support for emergency contraception in Mexico. Health care providers and clients greatly overestimated the negative health effects of emergency contraception, although clients overwhelmingly reported that they would use or recommend it if needed. Although providers typically advocated medically controlled distribution, clients believed emergency contraception should be more widely available, including in schools and vending machines with information prevalent in the mass media and elsewhere.

PIP: An interview was conducted to ascertain knowledge, attitudes, and practices concerning emergency contraception (EC) among health care providers and potential EC users in metropolitan Mexico. Findings showed that there was a limited knowledge about EC per se and its method, but nevertheless, most of the participants were cautious to support EC in Mexico. Health care providers and clients greatly overestimated the negative health effects of EC, although clients overwhelmingly reported that they would use or recommend it if needed. Although providers typically advocated medically controlled distribution, clients believe EC should be more widely available, including in schools and vending machines, with information prevalent in the mass media and elsewhere.

Dialysis kinetics of homocysteine and reactive oxygen species.

In patients with chronic renal failure who undergo hemodialysis (HD), the antioxidant system is inadequate to correct the imbalance between the generation and scavenging of reactive oxygen species. To clarify the role of six different membranes on oxidative stress, the authors measured plasma lipid peroxidation and erythrocyte (E) concentrations of several antioxidant enzymes in 30 HD patients: 20 on bicarbonate HD, 4 on paired filtration dialysis, 3 on acetate free biofiltration, and 3 on hemodiafiltration. Before, during, and after the first session of the week (at times 0, 30, 60, and 120 min, end, and 30 min after end of HD), several blood samples were drawn. Plasma (P) homocysteine (HCY), cysteine (CYS), malondialdehyde (MDA), E-glutathione (GSH), glucose-6-phosphodehydrogenase, glutathione reductase (GR), glutathione peroxidase (GP), catalase (CAT), and superoxide dismutase (SOD) were determined. All six membranes (Hemophan [HEMO]; cellulose diacetate [DIAC]; acrylonitrile-69 [AN69]; polymethylmethacrylate [PMMA]; cuprammonium rayon [CURAY]; polysulfone plus hemophan [PS + HEMO]) induced a significant decrease in plasma lipid peroxidation (p < 0.001) and an increase in E-GSH, GR, GR + flavinadenine dinucleotide, GP, and SOD (p < 0.001). Some membranes, however, showed some peculiar effects on reactive oxygen species: HEMO is better than DIAC, as far as P-MDA and P-HCY are concerned; PMMA induces higher changes in E-GR and P-CYS than does HEMO; and patients chronically using PMMA and PS + HEMO membranes show the lowest P-HCY levels both before and after dialytic sessions. Based on these changes, implications as to the effects on vascular disorders could be derived.