Современные аспекты атерогенеза

The basic postulate of atherosclerosis etiology and pathogenesis has changed during the last decade. This study, carried out on the human aorta and coronary heart vessels collected on 64 autopsies performed shortly after demise. Those with with cardiovascular insufficiency and an atherosclerosic background from 31 to 69 years of age were taken into the study group. Apoptotic cells were identified using terminal deoxynucleotidyl transferase (TUNEL). The TUNEL-labeled nuclei were found mainly in the region of the plaque that shows a dense infiltration by macrophages. The death of foam cells at the edge of the lipid core shows both necrosis and apoptosis. The remnants of apoptotic nuclei are also present in the lipid core. Apoptosis plays a key role in regulation of cell accumulation during atherosclerosis. It suggests involvement of ICE in SMC death in fibrous regions of complex atheroma and in macrophage death in the lipid-rich core of the lesions.На протяжении последнего десятилетия основные постулаты этиологии и патогенеза атеросклероза претерпели значительные изменения. Наши исследования были проведены на аорте, коронарных артериях сердца и сонных артериях на этапе раннего патологоанатомического вскрытия у умерших в результате церебро- и кардиососудистых патологий на фоне атеросклероза. Апоптотические клетки были идентифицированы TUNEL-методом. Tакже был подтвержден апоптоз макрофагов, клеток гладкой мускулатуры и эндотелиальных клеток. TUNEL-положительные ядра преимущественно были обнаружены в области бляшки богатой макрофагами. Смерть пенистых клеток может быть вызвана как некрозом так и апоптозом. Остатки этого процесса присутствуют в некротическом ядре бляшки. Апоптотический процесс играет решающую роль в регулировании клеточных отложений, вызывает смерть клеточных элементов в области фиброзной капсулы, провоцируя дестабилизацию и разрыв бляшки

An alarm signal for the medical world addressed from the pathological anatomy service in the Republic of Moldova

Department of Morphopathology, Nicolae Testemitsanu State University of Medicine and Pharmacy Chisinau, the Republic of Moldova, Department of Microscopic Morphology/Histology, Angiogenesis Research Center, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaBackground: Maintaining the quality and safety of pathology services is crucial for the efficient delivery of health care. However, pathology is, perhaps, the least understood of the medical specialties. In particular, the scope of pathology and the integral role it plays in all areas of medicine are not well recognized even by some of those working in health care environments. Strategic partnerships have as the main goal the enlargement of collaborative research and partnership on national and international level, mainly, but not exclusively in European Research Area. There is a perceived need for improved management practices, use of new technologies, and increased use of some categories of the personnel. Issues with the employment program were mentioned, including tracking, matching people to jobs, training, and finding more opportunities. There was a call for greater visibility in the community (both medical and scientific). The problems facing pathology teaching and pathology teachers mirror those of most other medical disciplines, namely a lack of time and money, and competing pressures from many other sources. Conclusion: There is the danger of producing doctors who cannot explain disease to their patients, who abuse laboratories and who have no interest in pursuing pathology as a career, leading to a slow and possibly irreversible decline in pathology as a medical profession

evaluation of liver fibrosis concordance analysis between noninvasive scores apri and fib 4 evolution and predictors in a cohort of hiv infected patients without hepatitis c and b infection

Background. There is lack of data on the incidence of liver fibrosis (LF) progression in patients with human immunodeficiency virus (HIV) monoinfection and risk factors for LF. Methods. We performed an observational prospective study in a cohort of HIV-infected patients who had initiated highly active antiretroviral therapy (HAART). FIB-4 and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) were assessed. The concordance between the 2 scores was assessed by weighted kappa coefficient. Kaplan-Meier analysis was used to estimate the incidence of LF. Cox regression analysis was used to assess the predictors of transition. Results. A total of 1112 patients were observed for a mean of 2249 days of follow-up. The concordance between FIB-4 and APRI was moderate (kappa = .573). The incidence of transition to higher FIB-4 classes was 0.064 (95% confidence interval [CI], 0.056―0.072) per person-year of follow-up (PYFU), whereas the incidence of transition to higher APRI classes was 0.099 (95% CI, 0.089-0.110) per PYFU. The incidence of transition to FIB-4 >3.25 was 0.013 per PYFU (95% CI, 0.010-0.017) and 0.018 per PYFU (95% CI, 0.014―0.022) for APRI >1.5. In multivariate analyses, for transition to higher classes, HIV RNA level 3.25 and APRI> 1.5 as study outcomes. Conclusions. Overall, our results suggest a possible benefit associated with earlier HAART initiation, provided that the effectiveness of HAART is sustained and treatment with DDX is avoided

Прогностические показатели развития ювенильного идиопатического артрита

Department of Pediatrics, Nicolae Testemitanu State Medical and Pharmaceutical University, Congresul III al Medicilor de Familie din Republica Moldova, 17–18 mai, 2012, Chişinău, Republica Moldova, Conferinţa Naţională „Maladii bronhoobstructive la copii”, consacrată profesorului universitar, doctor habilitat Victor Gheţeul, 27 aprilie, Chişinău, Republica MoldovaJuvenile idiopathic arthritis (JIA) is a highly disabling disease that leads to functional and physical compromise by osteo-articulars lesions and premature mortality in systemic diseases, impacting medical, social and economic well-being. To determine the prognosis of development indices JIA, discriminant function (F) was used and clinical examination was performed which included studying the patient’s age at disease onset, disease duration, number of joints and laboratory tests included studying the radiological stage after Steinbrocker. The discriminant function was performed in a group of 51 patients diagnosed with JIA. Factors that influenced the favorable evolution of JIA were high patient age at the onset of disease, low disease duration, a low number of joints and radiological stages I-II after Steinbrocker. The presence of these factors allowed us to predict 72.4% of cases with a favorable outcome. On the other hand, young age at onset, long disease duration, a high number of joints and radiological stages III-IV after Steinbrocker were unfavorable prognostic factors. The presence of these indices allowed the estimation of adverse developments in 77.3% of cases.Ювенильный идиопатический артрит (ЮИА) является хроническим заболеванием, которое приводит к функциональной и физической недостаточности, костно-суставным повреждениям преждевременной смертности (при системном варианте), имеет медицинское, социальное и экономическое значение. Для определения прогнозирующих факторов развития ЮИА была использована математическая дискриминантная функция (F) с проведением клинического обследования, которое включало изучение возраста пациента в начале заболевания, длительность заболевания, количество болезненных суставов, а лабораторные исследования включали изучение радиологических стадий по Штейнброкеру. Дискриминантная функция была определена у 51 пациентов с ЮИА. Таким образом, факторы, влияющие на благоприятную эволюцию ЮИА, были: возраст старше 10 лет в начале заболевания, короткая длительность заболевания, малое число болезненных суставов и радиологические стадии I-II по Штейнброкеру. Наличие этих факторов позволило в 72,4% случаев прогнозировать благоприятный исход ЮИА. С другой стороны, малый возраст пациента в начале заболевания, большая длительность заболевания, большое количество болезненных суставов и радиологические стадии III-IV по Штейнброкеру были неблагоприятными прогностическими факторами. Присутствие этих показателей позволило прогнозировать неблагоприятный исход в 77,3% случаев

CDKN1A upregulation and cisplatin-pemetrexed resistance in non-small cell lung cancer cells

Cisplatin-pemetrexed is a frequently adopted first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) ineligible for biological therapy, notwithstanding its limited efficacy. In the present study, the RAL cell line, an epidermal growth factor receptor (EGFR)-wild-type, p53- and KRAS-mutated model of NSCLC, was used to investigate novel biomarkers of resistance to this treatment. Cells were analyzed 96 h (96 h-post wo) and 21 days (21 days-post wo) after the combined treatment washout. Following an initial moderate sensitivity to the treatment, the cell growth proliferative capability had fully recovered. Gene expression analysis of the resistant surviving cells revealed a significant upregulation of CDKN1A expression in the cells at 96-h post-wo and, although to a lesser extent, in the cells at 21 days-post wo, accompanied by an enrichment of acetylated histone H3 in its promoter region. CDKN1A was also upregulated at the protein level, being mainly detected in the cytoplasm of the cells at 96 h-post wo. A marked increase in the number of apoptotic cells, together with a significant G1 phase block, were observed at 96-h post wo in the cells in which CDKN1A was knocked down, suggesting its involvement in the modulation of the response of RAL cells to the drug combination. On the whole, these data suggest that CDKN1A plays a role in the response to the cisplatin-pemetrexed combination in advanced KRAS-mutated NSCLC, thus suggesting that it may be used as a promising predictive marker

Effectiveness of service screening: a case–control study to assess breast cancer mortality reduction

The aim of this study was the evaluation of the impact of service screening programmes on breast cancer mortality in five regions of Italy. We conducted a matched case–control study with four controls for each case. Cases were defined as breast cancer deaths occurred not later than 31 December 2002. Controls were sampled from the local municipality list and matched by date of birth. Screening histories were assessed by the local, computerised, screening database and subjects were classified as either invited or not-yet-invited and as either screened or unscreened. There were a total of 1750 breast cancer deaths within the 50 to 74-year-old breast cancer cases and a total of 7000 controls. The logistic conditional estimate of the cumulative odds ratios comparing invited with not-yet-invited women was 0.75 (95% CI: 0.62–0.92). Restricting the analyses to invited women, the odds ratio of screened to never-respondent women corrected for self-selection bias was 0.55 (95% CI: 0.36–0.85). The introduction of breast cancer screening programmes in Italy is associated with a reduction in breast cancer mortality attributable to the additional impact of service screening over and above the background access to mammography

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART

Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE)

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/ mm3 plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection

BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling. The aim of this study was to elucidate the expression and mechanism of LRP1 in hepatocellular carcinoma (HCC). METHODS: LRP1 expression in 4 HCC cell lines and 40 HCC samples was detected. After interruption of LRP1 expression in a HCC cell line either with specific lentiviral-mediated shRNA LRP1 or in the presence of the LRP1-specific chaperone, receptor-associated protein (RAP), the role of LRP1 in the migration and invasion of HCC cells was assessed in vivo and in vitro, and the expression of matrix metalloproteinase (MMP) 9 in cells and the bioactivity of MMP9 in the supernatant were assayed. The expression and prognostic value of LRP1 were investigated in 327 HCC specimens. RESULTS: Low LRP1 expression was associated with poor HCC prognosis, with low expression independently related to shortened overall survival and increased tumor recurrence rate. Expression of LRP1 in non-recurrent HCC samples was significantly higher than that in early recurrent samples. LRP1 expression in HCC cell lines was inversely correlated with their metastatic potential. After inhibition of LRP1, low-metastatic SMCC-7721 cells showed enhanced migration and invasion and increased expression and bioactivity of MMP9. Correlation analysis showed a negative correlation between LRP1 and MMP9 expression in HCC patients. The prognostic value of LRP1 expression was validated in the independent data set. CONCLUSIONS: LRP1 modulated the level of MMP9 and low level of LRP1 expression was associated with aggressiveness and invasiveness in HCCs. LRP1 offered a possible strategy for tumor molecular therapy