Prospects of an alternative treatment against Trypanosoma cruzi based on abietic acid derivatives show promising results in Balb/c mouse model.

Chagas disease, caused by the protozoa parasite Trypanosoma cruzi, is an example of extended parasitaemia with unmet medical needs. Current treatments based on old-featured benznidazole (Bz) and nifurtimox are expensive and do not fulfil the criteria of effectiveness, and a lack of toxicity devoid to modern drugs. In this work, a group of abietic acid derivatives that are chemically stable and well characterised were introduced as candidates for the treatment of Chagas disease. In vitro and in vivo assays were performed in order to test the effectiveness of these compounds. Finally, those which showed the best activity underwent additional studies in order to elucidate the possible mechanism of action. In vitro results indicated that some compounds have low toxicity (i.e. >150 µM, against Vero cell) combined with high efficacy (i.e. <20 µM) against some forms of T. cruzi. Further in vivo studies on mice models confirmed the expectations of improvements in infected mice. In vivo tests on the acute phase gave parasitaemia inhibition values higher those of Bz, and a remarkable decrease in the reactivation of parasitaemia was found in the chronic phase after immunosuppression of the mice treated with one of the compounds. The morphological alterations found in treated parasites with our derivatives confirmed extensive damage; energetic metabolism disturbances were also registered by (1)H NMR. The demonstrated in vivo activity and low toxicity, together with the use of affordable starting products and the lack of synthetic complexity, put these abietic acid derivatives in a remarkable position toward the development of an anti-Chagasic agent.

Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

BACKGROUND AND OBJECTIVE: The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions. MATERIAL AND METHODS: A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists. RESULTS: Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis. CONCLUSION: The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

Bisphosphonate-associated osteonecrosis of the jaw 2 years after teeth extractions: a case report solved with non-invasive treatment.

Bisphosphonates are a type of drugs known to inhibit bone resorption through complex interventions. Their primary mechanism of action is aimed at the cellular level, inhibiting osteoclast activity and, thus, bone resorption. Bisphosphonates are, therefore, very widely used, with many patients receiving continuous treatment for years. But it is well known that these drugs can produce osteonecrosis of the jaw and this is their principal risk. A 75-year-old woman received dental treatment before starting intravenous BP therapy for a breast cancer. She started intravenous bisphosphonate treatment with monthly protocol and after two years the patient presented a wound compatible with osteonecrosis of the jaw.

Early predictors of antiviral treatment response in liver transplant recipients with recurrent hepatitis C genotype 1.

The success of current antiviral treatment for hepatitis C virus (HCV) recurrence in liver transplant (LT) recipients remains limited. We aimed at evaluating the value of IL28B genotype and early viral kinetics to predict response to standard treatment in the transplant setting. We retrospectively evaluated 104 LT recipients treated for HCV genotype 1 recurrence between 2001 and 2010. Baseline variables, including IL28B genotype, and early viral kinetics were compared among patients who did or did not achieve a sustained virological response (SVR). Logistic regression analyses of candidate variables were conducted to generate a reliable predictive model based on the minimum set of variables. Twenty-nine (28%) achieved an SVR. On multivariate analysis, the magnitude of HCV RNA decline at 4 weeks (OR: 3.74, 95% CI: 1.64-9.39; P = 0.003) and treatment compliance (OR: 35.27, 95% CI: 3.35-365.54; P = 0.003) were the only independent predictors of SVR. Favourable recipient IL28B genotype significantly correlates with virological response at week 4 (OR 3.23; 95% CI, 1.12-9.15; P = 0.03). By logistic regression analysis, a model including donor age, recipient rs12979860 genotype and viral load at 4 weeks showed the best predictive value for SVR with an area under the receiver operating curve of 0.861. Favourable recipient IL28B genotype strongly correlates with the viral response at week 4 which is the strongest predictor of response. The combination of recipient IL28B genotype and donor age with the week 4 response reliably estimates the probability of SVR early on-treatment and may facilitate therapeutic strategies incorporating new antiviral agents.

IL28B genetic variation and hepatitis C virus-specific CD4(+) T-cell responses in anti-HCV-positive blood donors.

Epidemiological, viral and host factors are associated with the outcome of hepatitis C virus (HCV) infection, and strong host immune responses against HCV favour viral clearance. Recently, genome-wide association studies have shown a strong correlation between single-nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene and spontaneous or treatment-induced HCV clearance. We have investigated whether protective IL28B genetic variants are associated with HCV-specific T-cell responses among Spanish blood donors. The rs12979860 IL28B haplotype was determined in 69 anti-HCV-positive blood donors (21 HCV RNA negative and 48 HCV RNA positive) and 30 seronegative donors. In all cases, HCV-specific CD4(+) T-cell responses to HCV recombinant proteins (core, NS3 and NS3 helicase) were assessed by ex vivo interferon-γ ELISpot assay. The rs12979860-CC genotype was highly overrepresented in donors with spontaneous HCV clearance when compared to those with chronic infection (76.2%vs 29.2%, P < 0.001; odds ratio, 7.77; 95% confidence interval, 2.4-25.3, P < 0.001). HCV-specific CD4(+) T-cell responses were detected in 16 (76.2%) spontaneous resolvers especially towards nonstructural proteins, but with no correlation with IL28B genotype. Chronic individuals had a significantly lower overall T-cell response again irrespective of IL28B genotype. When spontaneous resolvers and chronic individuals were stratified according to their IL28B genotype, significantly stronger T-cell responses were only observed among those with non-CC haplotypes. Although the protective rs12979860 IL28B CC genotype is associated with spontaneous HCV clearance, stronger CD4(+) T-cell responses towards NS3 were only evident among those with non-CC haplotypes.

Reversal of nonstructural protein 3-specific CD4(+) T cell dysfunction in patients with persistent hepatitis C virus infection.

Hepatitis C virus (HCV)-specific T cell responses are essential for HCV control, and chronic infection is characterized by functionally altered antigen-specific T cells. It has been proposed that the early inactivation of specific CD4(+) T cell responses may be involved in establishment of HCV persistence. We have investigated whether HCV-specific CD4(+) T cells dysfunction can be reversed in vitro. Nonstructural protein 3 (NS3) and core-specific CD4(+) T cells from eight chronically infected and eight spontaneously resolved HCV individuals were selected through transient CD154 (CD40 ligand) expression, and their functional profile (IFN-γ, IL-2, TNF-α, IL-10 and IL-4 production by enzyme-linked immunospot assay, cytometric bead array and intracellular cytokine staining, and proliferation by carboxy-fluorescein diacetate succinimidyl ester dilution assay) was determined both ex vivo and after in vitro expansion of sorted CD154-expressing cells in the absence of specific antigen in IL-7/IL-15-supplemented medium. Ex vivo bulk CD4(+) T cells from chronic patients expressed CD154 in most cases, albeit at lower frequencies than those of resolved patients (0.11%vs 0.41%; P = 0.01), when stimulated with NS3, but not core, although they had a markedly impaired capacity to produce IL-2 and IFN-γ. Antigen-free in vitro expansion of NS3-specific CD154(+) cells from chronic patients restored IFN-γ and IL-2 production and proliferation to levels similar to those of patients with spontaneously resolved infection. Hence, NS3-specific CD4(+) T cell response can be rescued in most chronic HCV patients by in vitro expansion in the absence of HCV-specific antigen. These results might provide a rationale for adoptive immunotherapy.

Femtosecond laser microstructuring of zirconia dental implants.

This study evaluated the suitability of femtosecond laser for microtexturizing cylindrical zirconia dental implants surface. Sixty-six cylindrical zirconia implants were used and divided into three groups: Control group (with no laser modification), Group A (microgropored texture), and Group B (microgrooved texture). Scanning electron microscopy observation of microgeometries revealed minimal collateral damage of the original surface surrounding the treated areas. Optical interferometric profilometry showed that ultrafast laser ablation increased surface roughness (R(a), R(q), R(z), and R(t)) significantly for both textured patterns from 1.2 x to 6 x-fold when compared with the control group (p < 0.005). With regard to chemical composition, microanalysis revealed a significant decrease of the relative content of contaminants like carbon (Control 19.7% ± 0.8% > Group B 8.4% ± 0.42% > Group A 1.6% ± 0.35%) and aluminum (Control 4.3% ± 0.9% > Group B 2.3% ± 0.3% > Group A 1.16% ± 0.2%) in the laser-treated surfaces (p < 0.005). X-ray diffraction and Raman spectra analysis were carried out to investigate any change in the crystalline structure induced by laser processing. The original predominant tetragonal phase of zirconia was preserved, whereas the traces of monoclinic phase present in the treated surfaces were reduced (Control 4.32% > Group A 1.94% > Group B 1.72%) as the surfaces were processed with ultrashort laser pulses. We concluded that femtosecond laser microstructuring offers an interesting alternative to conventional surface treatments of zirconia implants as a result of its precision and minimal damage of the surrounding areas.

Melatonin in diseases of the oral cavity.

BACKGROUND: Melatonin is the principal secretory product of the pineal gland. It has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a co-adjuvant in the treatment of certain conditions of the oral cavity. METHODS: An extensive review of the scientific literature was carried out using PubMed, Science Direct, ISI Web of Knowledge and the Cochrane base. RESULTS: Melatonin, which is released into the saliva, may have important implications for oral diseases. Melatonin may have beneficial effects in certain oral pathologies including periodontal diseases, herpes viral infections and Candida, local inflammatory rocesses, xerostomia, oral ulcers and oral cancer. CONCLUSIONS: Melatonin may play a role in protecting the oral cavity from tissue damage caused by oxidative stress. The experimental evidence suggests that melatonin may have utility in the treatment of several common diseases of the oral cavity. However, more specific studies are necessary to extend the therapeutic possibilities to other oral diseases.

Development of a clinical hepatic encephalopathy staging scale.

AIM: To develop a scale to assess the severity of hepatic encephalopathy using simple dichotomic items. METHODS: A list of 48 items was created by selecting items that are simple to recognize and categorize; it was applied to thirty-six cirrhotic in-patients with episodic encephalopathy, in addition to the adapted-West-Haven Criteria and the Glasgow Coma Score. The list underwent an item reduction process and principal component analysis; the metric characteristics were evaluated. RESULTS: Multiple neurological abnormalities were observed and a Clinical Hepatic Encephalopathy Staging Scale of nine items was constructed. The principal component analysis of the Clinical Hepatic Encephalopathy Staging Scale obtained two factors that explained 77% of the variance. The Clinical Hepatic Encephalopathy Staging Scale exhibited adequate internal consistency and reproducibility. The scores of the Clinical Hepatic Encephalopathy Staging Scale correlated to those of adapted-West-Haven Criteria and the Glasgow Coma Score. CONCLUSIONS: This study confirms that the evaluation of multiple neurological manifestations is not necessary to classify hepatic encephalopathy adequately, which can be simply undertaken by an assessment of the patient's orientation, alertness, ability to respond to commands and to talk. A list of nine items is proposed as a linear scale from normality (Clinical Hepatic Encephalopathy Staging Scale = 0) to deep coma (Clinical Hepatic Encephalopathy Staging Scale = 9).

Specificity of frontal dysfunctions in relapsing-remitting multiple sclerosis.

Various studies have reported deficits in frontal cognitive functions in patients with multiple sclerosis (MS). However, the frontal deficit is not uniform and is often very subtle. The aim of this study was to assess frontal functions in a broad sample of patients with relapsing-remitting multiple sclerosis at the mild-to-moderate stage. The sample included a series of 165 patients. We used a test battery covering the frontal functions that have been described as being altered in MS. Significant differences were found between the patient group and healthy controls on the WAIS Arithmetic subtest, the PASAT, category word recall and the number of trials required to reach the first category of the WCST. In conclusion, we observed significant differences with respect to the control group in terms of information processing speed and working memory. These functions involve connections between the frontal lobe and other brain regions.

Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patients.

Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV)-HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 microg/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4-12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects.

Hepatotoxicity of antiretroviral drugs in HIV HCV patients with congenital coagulopathies followed at an Haemophilia Unit during a decade.

The aim of the study was to assess the incidence and the cumulative probability of cytolytic and cholestatic hepatotoxicity during antiretroviral treatment in a group of HIV HCV haemophiliacs. We evaluated 47 patients that received 246 courses of antiretroviral treatment [98 courses of pre-highly active antiretroviral therapy (pre-HAART) and 148 HAART treatments]. Liver function tests were assessed at baseline of each treatment, after 1 month and at least every 4 months thereafter. Cytolytic and cholestatic hepatotoxicity was recorded. Of the 246 treatments, 28 (12.45%) were followed by cytolytic hepatotoxicity and 32 (13%) by cholestatic hepatotoxicity. Cytolytic hepatotoxicity was similar in HAART (16/148; 10.8%) and in pre-HAART treatment (12/98; 12.2%) and cholestatic hepatotoxicity was more frequent in HAART (29/148; 19.6%) than in pre-HAART treatment (3/98; 3.1%) (P < 0.001). The actuarial probability of developing cytolytic and cholestatic hepatotoxicity at 10 years of onset of antiretroviral treatments was 39% and 56%, respectively. Most enzyme elevations were asymptomatic, but in eight cases therapy was discontinued or changed and in one case a cirrhotic patient died of progressive liver failure. In HIV HCV haemophiliacs, the cumulative probability of developing hepatotoxicity during follow-up is high and although in the most cases the toxicity is mild, fatal cases can occur.

Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients with acute and chronic HBV infection.

This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes (A-F) and their association with the G1896A precore mutation in 486 patients positive for HBV surface antigen. Genotypes were determined by RFLP and precore mutation by real-time PCR. Genotypes D (48.1%) and A (39.5%) were the most common, followed by F (4.1%) and B, C and E (<1%). The A to D ratio (A:D) was 1.4 in HBeAg+ chronic hepatitis B (CHB), 0.6 in HBeAg- CHB and 1.4 in HBeAg- inactive carriers. Distribution of these genotypes was different between HBeAg+ CHB and HBeAg- CHB (P = 0.02), and between HBeAg- CHB and HBeAg- inactive carriers (P = 0.009). Genotype A was the most prevalent in HBeAg+ CHB with elevated alanine aminotransferase (ALT) (68.6%) and genotype D in HBeAg+ CHB with fluctuating ALT (60.7%). There was a difference in genotype prevalence between chronic and acute infection (P = 0.03). The precore mutant correlated with high levels of HBV-DNA in genotype d HBeAg- CHB. Genotype D is not as highly prevalent in Spanish patients as would be expected in a Mediterranean area. The unequal prevalence of genotypes between acute and chronic infection suggests that genotype A is associated with a higher tendency to cause chronic infection.

Changes in different regions of hepatitis B virus gene in hepatitis B 'e' antigen-negative patients with chronic hepatitis B: the effect of long-term lamivudine therapy.

BACKGROUND: Lamivudine therapy for chronic hepatitis B has been associated with changes in different regions of the hepatitis B virus nucleotide sequence. AIM: To study changes in the sequences of polymerase and precore/core promoter regions of hepatitis B virus, before and during 5 years of therapy with lamivudine. METHODS: Eighty consecutive samples were taken from 10 chronic hepatitis B 'e' antigen-negative patients. RESULTS: Nine patients carried hepatitis B virus precore mutations during the study. Before therapy, wild type was replaced by A1896 in two (20%) cases. During treatment, A1896 reverted transitory to wild type in five cases (50%) and in one case wild type was replaced by A1896. The continuous detection of precore mutations during therapy was associated with a lower response rate. YMDD mutations were observed in nine cases and both, L180M and M204V/I mutations were simultaneously detected in six cases. About 75% of the patients with M204V mutations were responders and none with M204I or mixed pattern sustained response. CONCLUSION: Hepatitis B 'e' antigen-negative patients exhibit changes in the precore regions both spontaneously and under lamivudine therapy, the transitory reversion to wild type being most frequently witnessed. Patients carrying M204V mutations are more likely to respond to therapy. If, in further studies, these results are confirmed some patients with YMDD mutations could benefit from prolonging the duration of lamivudine therapy.

Analysis of INF-gamma, TNF-alpha and dendritic cells to predict hepatitis C virus recurrence in liver transplant patients.

INTRODUCTION: Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease and the reason for more than 50% of liver transplantations (OLT). Recurrent HCV infection occurs in almost all transplant recipients and has an unfavorable course. Although immunosuppressive agents are necessary to avoid allograft rejection, these drugs may favor viral replication facilitating viral-mediated graft injury. METHODS: To predict the evolution of two HCV(+) patients who underwent OLT, we studied INF-gamma and TNF-alpha production and the maturation capacity of dendritic cells (DCs) at three time points: before transplantation (Pre-Tx) and at 2 (2M) and 6 (6M) months after transplantation. Cytometric bead assays were used to quantify INF-gamma and TNF-alpha production in the supernates of mixed leukocyte reactions (MLR) between spleen cells from the liver donor and CD4(+) cells from the recipients. Immature and mature DCs were generated in vitro from patient monocytes. RESULTS: The one patient who experienced recurrent HCV showed loss of CD4(+) responses to donor antigens and INF-gamma and TNF-alpha production after OLT. In contrast, the other patient maintained detectable levels of these cytokines after OLT. It was possible to generate mature DCs from monocytes with the aid of CD40L in both cases, but decreased expression of HLA-DR, CD80, and CD86 markers was observed upon posttransplantation analyses in the patient with recurrent HCV. CONCLUSION: Loss of the proliferative response as well as INF-gamma and TNF-alpha production, together with a decreased HLA-DR, CD80, and CD86 (markers of mature DCs), indicated an inadequate immune response to viral progression in the liver transplant recipient with relapsing HCV infection.

Subtype mutations in the envelope 2 region including phosphorylation homology domain of hepatitis C virus do not predict effectiveness of antiviral therapy.

The aim of this study was to determine whether specific sequences of the phosphorylation homology domain (PePHD) region could be correlated with differences in response to antiviral therapy in patients infected with hepatitis C virus subtypes 1b, 2c, 3a and 4c/d. We included 43 patients (22 sustained responders and 21 nonresponders or relapsers) in the study, who were classified according to early viral decline during the first weeks of antiviral treatment and response at end of follow up. Type of mutations, mutation frequency, genetic diversity and phylogenetic relationships were compared at the PePHD and flanking regions. Phylogenetic trees showed that each sequence clustered together with those of the same subtype. Sequences from subtypes 1b and 4c/d resembled more closely the phosphorylation sites of protein kinase R and eIF2 alpha than sequences from genotypes 2c and 3a, the latter with higher response rates to interferon-alpha (IFN alpha) treatment. However, within specific subtypes, no separate clusters of responders and nonresponders were observed either at the beginning or at the end of follow up. We were not able to find any particular sequence or mutation in the PePHD region or in any other subregion of the fragment studied that allowed prediction of treatment response.

Increased tumour necrosis factor alpha production in mesenteric lymph nodes of cirrhotic patients with ascites.

BACKGROUND: Cytokines produced in mesenteric lymph nodes of cirrhotic rats with bacterial translocation may participate in circulatory alterations of cirrhosis. AIM: To investigate whether cirrhotic patients present an increased local generation of cytokines in mesenteric lymph nodes. METHODS: Mesenteric lymph nodes from 26 cirrhotic and 10 control patients were assessed for tumour necrosis factor alpha (TNF) and interleukin 6 mRNA and protein expression by competitive reverse transcription-polymerase chain reaction, and by enzyme immunoassay and immunohistochemistry, respectively. RESULTS: Interleukin 6 levels were not different between cirrhotics and controls. Protein and mRNA TNF levels in mesenteric lymph nodes from cirrhotics were higher than in controls (p<0.05). Tissue expression of TNF by immunohistochemistry was more abundant in cirrhotics. Ascitic patients showed higher TNF levels (47 (34-54) pg/mg protein) than patients without ascites (18 (17-25) pg/mg protein) (p<0.001). Elevated TNF levels (>28 pg/mg protein) in cirrhotics were associated with a higher Child-Pugh score, the antecedent of ascites, a lower prothrombin rate, and higher bilirubin and blood TNF levels. The strongest association, confirmed by multivariate analysis, was with the presence of ascites (p<0.001). Bacterial infections after transplantation, mainly by enteric bacteria, were only detected in patients with high TNF levels in mesenteric lymph nodes (33% of patients; p=0.05). CONCLUSION: Patients with advanced liver cirrhosis, and especially with ascites, have increased local production of TNF in mesenteric lymph nodes that, in common with experimental cirrhosis, may also be induced by bacterial translocation.

Role of immunosuppression in the development of quinolone-resistant Escherichia coli spontaneous bacterial peritonitis and in the mortality of E. coli spontaneous bacterial peritonitis.

BACKGROUND: Norfloxacin decreases the incidence of spontaneous bacterial peritonitis in cirrhotics, but promotes the appearance of quinolone-resistant Escherichia coli. AIM: : To define the characteristics of quinolone-resistant E. coli spontaneous bacterial peritonitis. METHODS: E. coli-positive ascitic fluid cultures were identified during a 6-year period. Data on quinolone-sensitive and quinolone-resistant E. coli spontaneous bacterial peritonitis were compared. RESULTS: One hundred and two E. coli-positive ascitic fluid cultures were detected. Cirrhotics accounted for 67 cases. Spontaneous bacterial peritonitis was found in 47 of the 67 (70%) cases [35 (74%) caused by quinolone-sensitive and 12 (26%) caused by quinolone-resistant E. coli]. Norfloxacin prophylaxis was higher in the quinolone-resistant group (92% vs. 6%, P < 0.001). Compared with patients with quinolone-sensitive E. coli spontaneous bacterial peritonitis, those with quinolone-resistant E. coli spontaneous bacterial peritonitis showed a higher prevalence of associated immunosuppressive factors (immunosuppressive drugs, human immunodeficiency virus infection or cancer) (92% vs. 20%, P < 0.001). Steroid therapy was independently associated with quinolone-resistant E. coli spontaneous bacterial peritonitis (odds ratio, 49; 95% confidence interval, 3.4-699; P = 0.004). The Child-Pugh score (P = 0.03), immunosuppression (P = 0.02) and renal failure (P = 0.01) were independent predictors of E. coli spontaneous bacterial peritonitis-related mortality. CONCLUSIONS: Associated immunosuppression is an important co-factor for the development of quinolone-resistant E. coli spontaneous bacterial peritonitis and for E. coli spontaneous bacterial peritonitis-related mortality.

[Study of hepatitis B virus replication and infection by other hepatitis viruses in patients with chronic hepatitis B virus infection]. / Estudio de la replicación del virus de la hepatitis B e infección por otros virus hepatotropos en pacientes con infección crónica por el virus B.

AIM: To study hepatitis B virus (HBV) replication in a series of patients with HBV infection and to analyze the frequency of associated hepatitis C virus (HCV) and hepatitis D (HDV) infection. PATIENTS AND METHOD: Serological markers of HBV, HCV and HDV, transaminase values and HBV DNA were studied in serum samples from 463 patients with chronic HBV infection. RESULTS: Three hundred ninety-six (85.5%) were classified as hepatitis B, 33 (7.1%) as hepatitis B and C, 17 (3.6%) as hepatitis B and D and 17 (3.6%) as hepatitis B, C and D. Sixty-seven percent of patients with hepatitis B and 33% of those with chronic hepatitis B were asymptomatic HBsAg carriers. HVB DNA was identified in 27.7% of patients with hepatitis B, in 24% of those with hepatitis B and C, in 11.7% of those with hepatitis B and D and in 29.4% of those with hepatitis B, C and D. HBV DNA and elevated transaminase levels were found in 63% of HBeAg-positive patients and in only 16% of those who were anti-HBe-positive. These latter were considered candidates for antiviral treatment. CONCLUSIONS: In our environment, most patients with HBV infection are asymptomatic HBsAg carriers. Viral replication and elevated alanine aminotransferase levels were found in 22% of the patients. Consequently, these patients are candidates for antiviral treatment. Between 3.6% and 7.1% of patients with hepatitis B presented coinfection with HCV or HDV, or both. No significant differences were found in HBV replication among the different groups.

Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic patients.

Apolipoprotein E epsilon4 and ACE genes have been related to several conditions involving cognitive impairment, including Alzheimer's disease, normal ageing and cerebrovascular disease. However, it has not been established whether their genotypes are associated with alcoholism or its cognitive functioning. Genotypic distributions of 140 chronic alcoholic patients were compared with a non-alcoholic sample, and the cognitive performance of a subsample of the alcoholic subjects was assessed with standard neuropsychological tests. No differences in allele or genotype distributions of Apo E or ACE genes were found when comparing controls and alcoholics (Apo E epsilon2/2; patients 1.4%, controls 0% p < 0.06; epsilon2/epsilon3; patients 9.3%, controls 6.6% p < 0.29; epsilon2/epsilon4; patients 0%, controls 1% p < 0.31; epsilon3/epsilon3 patients 71.4%, controls 72% p < 0.89; epsilon3/epsilon4; patients 15.7%, controls 19.2%, p < 0.36; epsilon4/epsilon4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%, controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I; patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance, epsilon4/epsilon3 patients did better on visuoconstructive (p < 0.001) and visual memory (p < 0.04) functions compared with epsilon2/epsilon3 bearers. Furthermore, ACE D/D patients performed better on a test of abstract reasoning (p < 0.03) compared with the ACE I/I homozygous group. The cognitive results suggest that Apo E or ACE genotypes may modify the effects of ethanol on cognitive deterioration in alcoholic patients. However, the data do not support an association between the Apo E epsilon4 allele and reduced cognitive performance in alcoholism.