Quantification of serum markers of hepatitis B (HBV) and Delta virus (HDV) infections in patients with chronic HDV infection.

The interplay between hepatitis B (HBV) and delta (HDV) viruses is complex and not always characterized during chronic HDV infection. We assessed the clinical usefulness of new quantitative assays for HBV and HDV serum markers in a retrospective cross-sectional study. Sera obtained from 122 HDV genotype 1 and HBV genotype D coinfected, anti-HIV-negative patients (71 males; median age 49.8 [21.7-66.9] years), recruited consecutively in two geographical areas (Italy 69 patients, Romania 53 patients) with different HBV and HDV epidemiology, were tested for HBsAg, HBV-DNA, HBcrAg, total anti-HBc, HDV-RNA, IgM and total anti-HDV using quantitative assays. Cirrhosis, which showed comparable prevalence in the two cohorts, was diagnosed in 97 of 122 (79.5%) patients. At multivariate analysis, cirrhosis was associated with lower total anti-HBc/IgM anti-HDV ratio (OR 0.990, 95% CI 0.981-0.999, P = .038), whereas disease activity was associated with higher total anti-HDV (OR 10.105, 95% CI 1.671-61.107, P = .012) and HDV-RNA levels (OR 2.366, 95% CI 1.456-3.844, P = .001). HDV-RNA serum levels showed a positive correlation with HBV-DNA (ρ = 0.276, P = .005), HBsAg (ρ = 0.404, P < .001) and HBcrAg (ρ = 0.332, P < .001). The combined quantitative profiling of HBV and HDV serum markers identifies specific patterns associated with activity and stage of chronic hepatitis D (CHD). HDV pathogenicity depends on the underlying active HBV infection in spite of the inhibition of its replication. HDV-RNA, IgM anti-HDV, total anti-HDV, total anti-HBc, HBsAg and HBcrAg serum levels qualify for prospective studies to predict progressive CHD and identify candidates to antiviral therapy.

Factors That May Enhance Longevity: A Literature Review and a Comprehensive Update for Aesthetic Surgeons.

INTRODUCTION: After surgery, the plastic surgeon is very often questioned about how to maintain the result and more frequently how to slow down the aging process. However, this type of knowledge is not commonly delivered during medical education or at least needs an update. This review could be used as a guide to help plastic surgeons to manage these frequent postoperative consultations. The aim of this literature review was to focus discussion on specific positive factors, identified to have a significant impact on human longevity. MATERIALS AND METHODS: A literature review was performed using the automated computerized PubMed search, with the keywords "human longevity." Only papers written in the English language were included. References were screened to identify further relevant articles. Experimental studies based on microorganisms and animals, works published in non-indexed journals, case reports, letters, and viewpoints were excluded. RESULTS: One hundred and twenty-four articles reporting factors influencing human longevity were analyzed for data extraction. A total of 59 articles reporting only positive factors were included. Fourteen factors seemed to have a positive impact on longevity: caloric restriction, active effort and sports, happiness, vitamins, vegetarian or Mediterranean diet, oriental practices, socioeconomic status, genetics, sexual activity, sleep, moderate wine consumption, religion, and education. CONCLUSION: While some factors with a positive impact on longevity are clearly identified and should be integrated in the postoperative process, further studies are still needed to be able to slow down the aging process. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Optimization and critical evaluation of decellularization strategies to develop renal extracellular matrix scaffolds as biological templates for organ engineering and transplantation.

The ability to generate patient-specific cells through induced pluripotent stem cell (iPSC) technology has encouraged development of three-dimensional extracellular matrix (ECM) scaffolds as bioactive substrates for cell differentiation with the long-range goal of bioengineering organs for transplantation. Perfusion decellularization uses the vasculature to remove resident cells, leaving an intact ECM template wherein new cells grow; however, a rigorous evaluative framework assessing ECM structural and biochemical quality is lacking. To address this, we developed histologic scoring systems to quantify fundamental characteristics of decellularized rodent kidneys: ECM structure (tubules, vessels, glomeruli) and cell removal. We also assessed growth factor retention--indicating matrix biofunctionality. These scoring systems evaluated three strategies developed to decellularize kidneys (1% Triton X-100, 1% Triton X-100/0.1% sodium dodecyl sulfate (SDS) and 0.02% Trypsin-0.05% EGTA/1% Triton X-100). Triton and Triton/SDS preserved renal microarchitecture and retained matrix-bound basic fibroblast growth factor and vascular endothelial growth factor. Trypsin caused structural deterioration and growth factor loss. Triton/SDS-decellularized scaffolds maintained 3 h of leak-free blood flow in a rodent transplantation model and supported repopulation with human iPSC-derived endothelial cells and tubular epithelial cells ex vivo. Taken together, we identify an optimal Triton/SDS-based decellularization strategy that produces a biomatrix that may ultimately serve as a rodent model for kidney bioengineering.

Outcome of liver transplantation for hepatocellular carcinoma -- a single center experience.

BACKGROUND & AIMS: Liver transplantation (LT) is a promising treatment for patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). The aim of our study was to evaluate our experience regarding the clinical and pathological staging of HCC in patients who underwent LT, as well as recurrence free and overall survival. METHODS: From January 2006 to December 2011, 38 patients with diagnosis of HCC, underwent LT in our Center. Demographic, clinical, imaging and pathologic information were recorded. A Cox proportional hazards survival analysis was performed in order to identify significant predictors of tumor recurrence and patient's death after LT. RESULTS: Eighteen patients (47.4%) in our study group were within Milan criteria. The mean follow-up was 22 months and the recurrence rate of HCC after LT was 13.2%. The 1, 3- year recurrence free survival rates were 85%, 74.3% respectively. The 1 and 3-year overall survival rates were 83.5% and 63.6% respectively. No significant predictor for HCC recurrence was identified in our study group by survival analysis, taking into account 13 different variables. As independent predictors of patient'ss death after LT for HCC however, the presence of diabetes mellitus (p=0.001), presence of more than 3 HCC nodules (p=0.03) and tumor recurrence after LT (p=0.03) were identified by multivariate Cox proportional hazards survival analysis. CONCLUSION: In our cohort HCC recurrence rate after LT was 13.2%. Diabetes mellitus, presence of more than 3 HCC nodules and HCC recurrence were significant predictors of poor overall survival after LT.

Nutritional risk screening and prevalence of malnutrition on admission to gastroenterology departments: a multicentric study.

BACKGROUND AND AIMS: There is little awareness and a lack of data on the prevalence of hospital malnutrition in gastro-enterology departments. Since part of these patients are referred for surgical treatment and poor nutritional status is a known risk factor for perioperative morbidity, we conducted a prospective study aimed to screen for the nutritional risk and assess the prevalence and risk factors of malnutrition in gastro-enterology departments in Romania. METHODS: We included patients consecutively admitted to 8 gastroenterology units over a period of three months in our study. Nutritional risk was evaluated using NRS 2002. Malnutrition was defined using BMI ( 20 kg m2) or and 10% weight loss in the last six months. RESULTS: 3198 patients were evaluated, 51.6% males and 48.4% females, with the mean age of 54.5 Â+- 14.3 years. Overall percentage of patients at nutritional risk was 17.1%, with the highest risk for patients with advanced liver diseases (49.8%), oncologic (31.3%), inflammatory bowel diseases (20.2%), and pancreatic diseases (18.9%). The overall prevalence of malnutrition was of 20.4%, higher for advanced liver diseases (39.4%), inflammatory bowed diseases (30.6%), oncologic (26.8%) and pancreatic diseases (23%). Independent risk factors for malnutrition were younger age (p 0.0001), female gender (p 0.0001), a higher (A ≥ 3) NRS (p 0.0001), presence of neoplasm (p 0.0001), of advanced liver disease (p=0.0003) and a reduction of 25% of dietary intake (p 0.0001). CONCLUSIONS: One in five patients admitted to gastroenterology units could benefit from prompt nutritional intervention. Correction of nutritional status is mandatory before any surgical procedure. Emphasis on nutritional evaluation at admission and beginning of nutritional therapy where needed are particularly required in patients with advanced liver diseases, digestive neoplasms, inflammatory bowel diseases and pancreatic diseases. ABBREVIATIONS: NRS= nutritional risk score, BMI = body mass index, IBD = inflammatory bowel diseases.

Assessment of Minimal Hepatic Encephalopathy with Brain MRI and EncephalApp Stroop Test.

Background: Minimal hepatic encephalopathy (MHE) consists of subtle cognitive deficits that are not apparent on a standard neurological examination. Minimal hepatic encephalopathy has been reported in up to 80% of cirrhotic patients and is associated with decreased job performance, poor driving performance, impaired quality of life, and poor survival. In parallel, brain magnetic resonance imaging (MRI) abnormalities are known to occur in liver cirrhotic patients in the form of T1 globus pallidus hyperintensities. In recent years, a new psychometric test for diagnosing MHE has been developed as an app for smartphones and tablets (EncephalApp Stroop test). A translated version of the app is available in Romanian language. Aim:To use EncephalApp Stroop test for MHE diagnosis in our cirrhotic patients; to describe the main brain MRI abnormalities encountered in these patients; and to establish if Stroop test results correlate with imaging findings, clinical neurologic findings, and liver function parameters or prognosis. Material and methods:Cross-sectional study over a one-year period, involving 30 adult patients with liver cirrhosis. Subjects were evaluated through a standard neurological examination, psychometric testing using EncephalApp Stroop test, electroencephalogram and brain MRI. In parallel, 40 adult healthy controls were also recruited and evaluated with the EncephalApp Stroop test using the same methodology. Results:Age distribution was similar between the two groups (p=0.6). The mean age of patients was 50±10 years and that of controls 51±12 years. Mean Stroop result was 171±26 seconds for the patient group and 143±20 seconds for the control group (p<0.0001). There was a direct correlation between Stroop test results and age in the control group (R=0.69, p<0.0001) but not also in the patient group (R=0.28, p=0.13). Statistically significant results were obtained by using the Fischer exact test for both cut-off values: 145 seconds in patients < 45-year-old (p<0.001) and 190 seconds in those ≥45 years-old (p=0.03). MRI T1-hyperintensities of the basal ganglia, blood ammonia levels and electroencephalographic changes were not associated with poorer results. Conclusion:Our pilot study, although small, confirmed that patients with liver cirrhosis may have subtle deficits in cognitive areas like attention, concentration or reaction time. This can be assessed easily with the EncephalApp Stroop test which is readily available for use on smartphones or tablets.

[Liver transplantation--indications, surgical technique, results--the analysis of a clinical series of 200 cases]. / Transplantul hepatic--indicati, tehnica, rezultate-analiza unei serii clinice de 200 de cazuri.

INTRODUCTION: Initially considered experimental, liver transplantation (LT) has become the treatment of choice for the patients with end-stage liver diseases. MATERIAL AND METHODS: Between April 2000 and October 2009, 200 LTs (10 reLTs) were performed in 190 patients, this study being retrospective. There were transplanted 110 men and 80 women, 159 adults and 31 children with the age between 1 and 64 years old (mean age--39.9). The main indication in the adult group was represented by viral cirrhosis, while the pediatric series the etiology was mainly glycogenosis and biliary atresia. There were performed 143 whole graft LTs, 46 living donor LTs, 6 split LTs, 4 reduced LTs and one domino LT RESULTS: The postoperative survival was 90% (170 patients). The patient and graft one-year and five-year survivals were 76.9%, 73.6% and 71%, 68.2%, respectively. The early complications occurred in 127 patients (67%). The late complications were recorded in 71 patients (37.3%). The intraoperative and early postoperative mortality rate was 9.5% (18 patients). CONCLUSIONS: The Romanian liver transplantation program from Fundeni includes all types of current surgical techniques and the results are comparable with those from other international centers.

Current immunosuppressive approaches in liver transplantation.

A significant increase of potent immunosuppressive agents over the last two decades has contributed to improved patient and graft survival after liver transplantation (LT). Numerous ongoing studies aim to determine the most effective immunosuppressive protocols while minimizing drug-related side effects. These protocols often combine several drugs with different mechanisms of action and toxicities allowing dosage adjustment. There is also a trend towards tailored immunosuppressive regimens according to the etiology of liver disease and comorbidities such as renal dysfunction and cardiovascular disease. The introduction of antibody induction therapies and antimetabolites resulted in an increasing number of studies with steroid minimization and calcineurin inhibitor (CNI) reduction protocols. Combined mycophenolate mofetil and minimal dose CNI therapy has shown to be safe and to improve kidney function and cardiovascular risk profile in the majority of studies. Sirolimus (SRL) and everolimus constitute a new class of compounds designated as the mammalian target of rapamycin (mTOR) inhibitors, which exhibit immunosuppressive and antiproliferative effects. There are conflicting results with respect to renal improvement upon switch to mTOR inhibitor therapy with concomitant reduction/elimination of CNI. Further trials will determine whether earlier conversion to mTOR inhibitors enable prevention of CNI-related renal dysfunction. Future results from randomized controlled studies will also show whether SRL can improve recurrence-free survival in patients transplanted for hepatocellular carcinoma.

MELD exceptions and new predictive score of death on long waiting lists for liver transplantation.

BACKGROUND: Cirrhosis related complications, considered MELD exceptions, proved to add prognostic value to the MELD score in predicting waiting list mortality. AIM: To identify the predictive value for death on a long waiting list (WL) for the complications of liver disease. METHODS: During 2004-2007, 372 consecutive adult patients were listed for liver transplantation (LT). To identify the potential predictors of patient death, univariate and multivariate Cox's proportional hazards regression model was used. RESULTS: In the univariate survival analysis the following variables were significant: spontaneous bacterial peritonitis, refractory ascites, hyponatremia, hepatic encephalopathy, hepatorenal syndrome, initial and current MELD score, initial and current Child-Pugh score. The independent predictors of death on our WL were: refractory ascites (p=0.002) and hepatorenal syndrome (p=0.002). Based on a logistic regression analysis a new score has been developed: Score = 1/(1+ exp(-(-4.38 + 1.34 x Refractory ascites + 0.9 x Hepatorenal syndrome + 0.15 x Current MELD). The c-statistic for the new score for prediction of death on the WL was 0.85 compared to 0.80 for current MELD score. CONCLUSION: Refractory ascites and hepatorenal syndrome should add valuable points to the current MELD in order to better prioritize for LT patients included on long WL. ABBREVIATIONS: Liver transplantation (LT), Model for End-Stage Liver Disease (MELD), waiting list (WL), United Network for Organ Sharing (UNOS), standard deviation (SD), receiver operating characteristic (ROC), hepatitis B virus (HBV), hepatocellular carcinoma (HCC), positive predictive value (PPV), negative predictive value (NPV), Child-Turcotte-Pugh (CTP), hepatic venous pressure gradient (HVPG).

Stem cells therapies for gastrointestinal and liver diseases.

Stem cells therapies represent a new field of biomedical science which could provide in the future the cure for diseases until now incurable. The present paper reviews current knowledge on key biological properties of stem cells with focus on hepatic and gastrointestinal stem cells and current applications of stem cells therapies in gastrointestinal and liver diseases. Potential clinical applications for stem cells therapies have been suggested from animal model trials in acute liver failure, inherited metabolic liver disease and endstage liver disease (cirrhosis). Hematopoietic autologous stem cells transplantation has already been successfully performed in patients with severe inflammatory bowel disease or patients with refractory celiac disease with aberrant T cells. Future stem cells therapies for gastrointestinal postoperative or Crohn's disease fistulas are currently under investigation. More research is needed for perfecting stem cells harvesting protocols from different sources, in vitro expansion and differentiation protocols which can be used in phase II and III clinical trials.

Ribavirin with either standard or pegylated interferon to treat recurrent hepatitis C after liver transplantation.

AIM: To investigate the efficacy of two anti-viral protocols in hepatitis C virus-reinfected liver transplant recipients. METHODS: In this prospective study, 26 liver transplant patients were treated with standard interferon-alpha2b for 12 months or standard interferon-alpha2b for 3 months followed by pegylated interferon-alpha2b for 9 months. Interferon was combined with ribavirin in all patients. The histological course of the study population was compared with an untreated historic control group (n = 38) with similar baseline characteristics. RESULTS: The sustained virological response rates in the standard interferon group and in the pegylated interferon group were 27.3% and 26.7%, respectively. Only 29% of patients with sustained virological response had end of treatment histological response, whereas 47% of viral non-responders showed end of treatment histological response. The percentage of patients with histological improvement was significantly higher in the study population when compared to the controls. Univariate analysis indicated that hepatitis C virus genotype non-1, high baseline alanine aminotransferase, the time interval between liver transplant and interferon therapy and the body mass index predicted sustained virological response. In the multivariate model, baseline alanine aminotransferase and the body mass index remained a significant predictor of sustained virological response. CONCLUSIONS: Both treatment regimens offer similar efficacy profiles. Failure to eradicate hepatitis C virus should not lead to treatment discontinuation if serial liver biopsies demonstrate histological response.

Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor.

We have identified subtype selective agonists, partial agonists and antagonists, which distinguish the human recombinant Mel1a and Mel1b melatonin receptors expressed in COS-7 cells. Melatonin receptor agonists showed higher affinity for competition of 2-[125I]-iodomelatonin binding for the Mel1b than the Mel1a melatonin receptor. The dissociation constants (Ki) of 16 agonists determined on the recombinant human Mel1a and Mel1b melatonin receptor subtypes showed a significant correlation (r2 = 0.85, slope = 0.97, P < 0.0001, n = 16). However, six agonists showed 10 to 60 fold higher affinity for the Mel1b melatonin receptor as indicated by the affinity selectivity ratios (Mel1a/Mel1b) [8-methoxy-2-acetamidotetraline (11); S20098 (14); 8-methoxy-2-propionamidotetraline (20); 6, 7 di-chloro-2-methylmelatonin (21); 6-chloromelatonin (57); 6-methoxymelatonin (59)]. Dissociation constants for competition of 11 partial agonists and antagonist for 2-[125I]-iodomelatonin binding were between 15.5 (luzindole, pKi: 7.7) to 362 (4-phenyl-2-chloroacetamidotetraline, pKi: 9.1) fold higher for the Mel1b than for the Mel1a melatonin receptor. The lack of correlation between the pKi values (r2 = 0.23, P > 0.1, n = 11) strongly suggest that the two human melatonin receptor subtypes can be distinguished pharmacologically. The partial agonist: 5-methoxyluzindole (pKi: 9.6) and the competitive melatonin receptor antagonists: GR128107 (pKi: 9.6), 4-phenyl-2-chloroacetamidotetraline (pKi: 9.1), 4-phenyl-2-acetamidotetraline (pKi: 8.9) and 4-phenyl-2-propionamidotetraline (pKi: 8.8) are selective Mel1b melatonin receptor analogues as their affinity selectivity ratios (Mel1a/Mel1b) are bigger than 100. We conclude that the 40% overall amino acid difference in the sequence of the human recombinant Mel1a and Mel1b melatonin receptors is reflected in distinct pharmacological profiles for the subtypes. We compared the pharmacological profile of the presynaptic ML1 melatonin heteroreceptor of rabbit retina mediating inhibition of the calcium-dependent release of dopamine to that of the recombinant Mel1a and Mel1b melatonin receptors. Melatonin inhibited [3H]dopamine release by 50% (1C50) at 20 pM with a maximal inhibitory effect (80%) at 1 nM. The partial agonists, i.e., N-acetyltryptamine (1C50 5.6, maximal inhibition 55%) and 5-methoxyluzindole (1C50: 1.3, maximal inhibition 40%) showed various degrees of efficacy while none of the competitive melatonin receptor antagonists did inhibit [3H]dopamine release on their own. The potency (1C50) of full melatonin receptor agonists significantly correlated with their affinity to compete for 2-[125I]-iodomelatonin binding to either the Mel1a (r2 = 0.76, slope = 0.77, P < 0.0001, n = 17) or Mel1b (r2 = 0.63, slope = 0.75, P < 0.001, n = 17) human melatonin receptors. By contrast, the apparent dissociation constants (KB) for partial agonists and antagonists to antagonize the inhibition of [3H]dopamine release mediated by activation of the ML1 heteroreceptor by melatonin, significantly correlated with the affinity constants (Ki) for 2-[125I]-iodomelatonin binding determined of the Mel1b (r2 = 0.77, slope = 0.55, P < 0.001; n = 11) but not the Mel1a (r2 = 0.27, P < 0.1, n = 11) subtype. Together these results demonstrate that the pharmacological profile of the human recombinant Mel1b melatonin receptor is similar to that of the functional presynaptic melatonin heteroreceptor of rabbit retina, which we referred as an ML1B subtype. We conclude that the selective Mel1b melatonin partial agonists and antagonists described here can be used to identify melatonin receptor subtypes in native tissues and to search for subtype selective analogues with therapeutic potential.

Collapse of the N=28 shell closure in (42)Si.

The energies of the excited states in very neutron-rich (42)Si and (41,43)P have been measured using in-beam gamma-ray spectroscopy from the fragmentation of secondary beams of (42,44)S at 39A MeV. The low 2(+) energy of (42)Si, 770(19) keV, together with the level schemes of (41,43)P, provides evidence for the disappearance of the Z=14 and N=28 spherical shell closures, which is ascribed mainly to the action of proton-neutron tensor forces. New shell model calculations indicate that (42)Si is best described as a well-deformed oblate rotor.

Predictors of death on the waiting list for liver transplantation characterized by a long waiting time.

The number of patients dying while on the liver transplantation (LT) waiting list (WL) has continued to increase in recent years as a result of severe shortage of organs. Therefore, it is important to evaluate the existing models that predict death on the WL and to determine the independent predictors of death. The study cohort comprised 152 adult patients listed for LT in our centre over a period of 2 years (January 2001 to January 2003). The 12-month survival rate has been calculated by Kaplan-Meier method. The survival analysis performed by Cox proportional hazard model has evaluated the three parameters which compose the model for end-stage liver disease (MELD) score. Forty-four patients (28.9%) died while listed for LT. The survival rate was 92% at 3 months, 80% at 6 months and 69% at 12 months. Median survival was not reached. MELD score was found to be an excellent predictor of death at 12 months on our WL--c-statistic (area under curve) 0.84. In our survival analysis, only international normalized (prothrombin) ratio (INR) and serum creatinine were identified as an independent predictors of death (P < 0.0001). A new simplified version of the MELD score, which does not include serum bilirubin, is proposed and its c-statistic as predictor for death on the WL at 12 months is 0.86, as good as the original MELD score, when evaluated on our list. There is a fourfold increase in mortality on our WL for LT between 3 and 12 months after the inclusion. A simplified version of the MELD score, using only serum creatinine and INR might be taken into account when predicting 12 months mortality on WL with longer waiting time, but it has to be confirmed by other prospective studies.

[Research on phagocytosis]. / Investigarea fagocitozei.

A problem of particular importance, but also particularly difficult, is the investigation of the phagocytic system, considering its implication in various aspects of pathology. This has determined the authors to present the major modalities for the investigation of phagocytosis. They recommend as a diagnostic method for garnulocytopathies (including a series of metabolic abnormalities. Of the leucocytes with implications for the bactericidal capacity), a testing of leucocyte bactericidal capacity. The test with nitroblue tetrazolium is also recommended, for the screening and differential diagnosis of fever conditions of infectious origin and other etiologies.

Characterization of hydrazine-stimulated proteolysis in human erythrocytes.

The ability of hydrazine, acetylphenylhydrazine, methylhydrazine, and phenylhydrazine to stimulate proteolysis in red cells has been characterized. All four hydrazines effectively stimulated proteolysis in red cells and in hemolysate as evidenced by a two- to threefold increase in the rate of tyrosine release. The rate of tyrosine release varied linearly with time, increased with increasing concentration of hydrazine, and also increased as a function of hematocrit. The rank order for stimulation of proteolysis in red cells was phenylhydrazine greater than methylhydrazine greater than hydrazine approximately equal to acetylphenylhydrazine. Inhibitors of glycolysis in red cells only minimally (13-27%) decreased the rate of tyrosine release stimulated by the different hydrazines. Agents which diminished electron transport decreased the rate of tyrosine release. NADP inhibited the rate of tyrosine release stimulated by hydrazine, methylhydrazine, and acetylphenylhydrazine by approximately 36 to 41%; 2'-AMP was less effective. The rate of tyrosine release resulting from insult by the hydrazines was increased slightly by methylene blue, moderately inhibited (approximately 10 to 27%) by the chelator o-phenanthroline and inhibited approximately 30 to 40% by N-ethylmaleimide. Use of an oxygen-depleted atmosphere (N2) increased slightly the rate of tyrosine release stimulated by the hydrazines; in contrast, carbon monoxide decreased proteolysis stimulated by hydrazine, methylhydrazine, and acetylphenylhydrazine by approximately 50%. Although the antioxidants dimethylfuran, dimethylthiourea, and methylsulfoxide failed to diminish proteolysis stimulated by the hydrazines, N-acetylcysteine exerted a protective effect, decreasing hydrazine-stimulated tyrosine release in red cells approximately 30 to 50%. Inclusion of 3-amino-1,2,4-triazole in the incubation failed to increase further the rate of hydrazine-stimulated proteolysis. These data suggest that more reactive free radicals generated from the hydrazine are responsible for protein damage, that damaged protein (hemoglobin) is degraded via proteolysis, and that an ATP-independent process primarily participates in the degradation of abnormal proteins in the red cell. Thus, proteolytic enzymes present in the erythrocyte appear to exert a protective effect against cellular damage through the removal of abnormal proteins generated as a consequence of xenobiotic insult. The ability of proteolytic enzymes to recognize and degrade abnormal proteins may be of importance in using protein (hemoglobin)-xenobiotic adducts to assess exposure to toxic agents (risk assessment).

[Immunologic research in pediatrics]. / Investigatii imunologice în pediatrie.

The child, in his ontogenesis, repeats the phylogenetic evolution of the immune processes. The immunologic maturation gradually appears, the process having a definite duration. The immunologic maturation seems to be parallel to the maturation of other physiological processes. The immune system of the child is different from that of the adult, and the development features of his immune reactivity will give a specific evolution to his morbid manifestations.