Retinal Functional Impairment in Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a neurodegenerative disease of the retina. The aim of our study was to analyze latency changes in a full-field electroretinogram (ERG) in patients with type 2 diabetes. MATERIAL: This prospective study included 15 diabetic patients without DR, 16 diabetic patients with non-proliferative DR, 14 patients with pre-proliferative DR, 15 patients with proliferative DR, and 14 age-matched controls. All the participants underwent ophthalmologic examination and full-field ERGs. The ERGs were recorded with the Metrovision MonPackOne system. The latencies were analyzed for "a"- and "b"-waves in the dark-adapted (DA) 0.01 ERG, DA 3.0 ERG, DA oscillatory potentials, light-adapted (LA) 3.0 ERG, and 30 Hz flicker ERG. RESULTS: The delayed responses of healthy subjects compared to diabetic patients without DR were the DA oscillatory potentials (25.45 ± 1.04 ms vs. 26.15 ± 0.96 ms, p = 0.027). When comparing diabetic patients without DR and with non-proliferative DR, we did not obtain statistically significant delays. Significant delays in the DA 0.01 "b"-wave (61.91 ± 5.52 ms vs. 66.36 ± 8.12 ms, p = 0.029), DA 3.0 "b"-wave (41.01 ± 2.50 ms vs. 44.16 ± 3.78 ms, p = 0.035), and LA 3.0 "a"-wave (16.21 ± 0.91 ms vs. 16.99 ± 1.16 ms, p = 0.045) were found between non-proliferative DR and pre-proliferative DR. When comparing the groups of patients with pre-proliferative DR and proliferative DR, the LA 3.0 ERG "b"-wave (32. 63 ± 2.53 ms vs. 36.19 ± 3.21 ms, p < 0.0001), LA 30 Hz flicker ERG "a"-wave (19.56 ± 3.59 vs. 21.75 ± 4.74 ms, p= 0.025), and "b"-wave (32.23 ± 4.02 vs. 36.68 ± 3.48 ms, p = 0.017) were delayed. CONCLUSIONS: the electrophysiological findings from our study indicate that there is a substantial dysfunction of the neural retina in all stages of DR.

Multidisciplinary approach to patients with manifestations and pulmonary complications of cystic fibrosis.

Cystic fibrosis (CF) is a genetic disease, with autosomal recessive transmission, multisystemic, characterized by a remarkable clinical polymorphism and significant lethal prospective. Respiratory manifestations dominate the clinical picture, being present in all patients. The aim of the paper was to analyze the incidence of clinical manifestations, especially respiratory ones, as well as the contribution of interdisciplinary consultations to the positive diagnosis of CF, in a group of 16 patients who were hospitalized and treated in the IInd Pediatric Clinic and IInd Medical Clinic of the Emergency County Hospital, Craiova, Romania, in a period of 20 years. The 16 patients diagnosed with and treated of CF had all shown increased values of sweat chloride concentration of over 60 mmol∕L. The main symptoms and clinical signs encountered in these patients were cough (75%), sputum (62.5%), dyspnea (50%), wheezing (50%), stature hypotrophy (100%), pallor (37.5%), cyanosis (25%). All 16 patients had an acute exacerbation of chronic pulmonary disease. Of the total hospitalizations, the death was recorded only in the case of one female patient. The association of some clinical aspects specific with a positive result of the sweat test or the presence of the two pathological alleles made room for determining a positive diagnosis. The multisystemic nature of this disease requires a multidisciplinary approach to these patients. Histopathologically, there was a correspondence between lung morphological lesions and the results of imaging investigations.

Serum Biomarkers for Discrimination between Hepatitis C-Related Arthropathy and Early Rheumatoid Arthritis.

In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti-cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers. Serum samples were collected from 54 patients (30 diagnosed with eRA-subgroup 1 and 24 with HCVrA-subgroup 2) and from 28 healthy control persons. For the evaluation of serum concentrations of studied cytokines and auto-antibodies, we used immunoenzimatique techniques. The serum concentrations of both proinflammatory cytokines were statistically significantly higher in patients of subgroup 1 and subgroup 2, compared to the control group (p < 0.0001). Our study showed statistically significant differences of the mean concentrations only for ANA and IgG anti-CCP between subgroup 1 and subgroup 2. We also observed that IL-6 and TNF-α better correlated with auto-antibodies in subgroup 1 than in subgroup 2. In both subgroups of patients, ROC curves indicated that IL-6 and TNF-α have a higher diagnostic utility as markers of disease. In conclusion, we can say that, due to high sensitivity for diagnostic accuracy, determination of serum concentrations of IL-6 and TNF-α, possibly in combination with auto-antibodies, could be useful in the diagnosis and distinguishing between patients with true eRA and HCV patients with articular manifestation and may prove useful in the monitoring of the disease course.

Histological factors that predict the liver fibrosis in patients with chronic hepatitis C.

In chronic hepatitis, pathologies reveal a prominent inflammatory infiltrate portal consisting mostly of lymphocytes and plasma cells invading the portal spaces, although one can also identify macrophages, neutrophils or eosinophils. In all the forms of chronic hepatitis, fibrosis starts in the portal area, namely periportally, subsequently extends towards the lobules to the central veins, causing septa, followed by fibrosis. We studied 52 patients with chronic hepatitis C, who underwent a hematological, biochemical, virological and histopathological investigation. We found that the severity degree of the portal inflammation was in direct relation to the hepatitis activity index (HAI) and to the degree of fibrosis. The portal inflammation is dependent to the degree of fibrosis. The degree of inflammation significantly changes the distribution of cases with different degrees of fibrosis (chi-square p=0.00011 <0.001). Periportal inflammation, periportal necrosis and focal necrosis are the morphological aspects of the necroinflammatory process best correlated to the occurrence and development of fibrosis.

Targeting the VEGF and PDGF signaling pathway in glioblastoma treatment.

Growth factor receptors dysfunction has previously been correlated with glioma cell proliferation, ability to evade apoptosis, neo-angiogenesis and resistance to therapy. Antineoplastic molecules targeting growth factor receptors are in clinical handling, however the efficacy of these compounds has often been limited by the signaling redundancy. Here, we analyzed the effect of AG1433 (a PDGFR inhibitor), SU1498 (a VEGFR inhibitor) and BEZ235 (a PI3K/Akt/mTOR signaling pathways inhibitor) on glioblastoma cells in vitro. For this study, we used a low passage glioblastoma cell line (GB9B). Assessment of cell number over 72 h showed that the growth rate was 0.3024 and the doubling time of GB9B was 2.29 days. Similar cytotoxic effects were observed by using AG1433 and SU1498 treatment, while dual PI3K/Akt/mTOR inhibition by BEZ235 was more efficient in killing glioblastoma cells than individual PDGFR or VEGFR targeting. In SU1498 treated cells, caspase 3 activity was detected 3 hours after the treatment, while activation of caspase 8 and 9 was detected 48 hours later. AG1433 treatment induced caspase 3, 8 and 9, 3 hours after the treatment. BEZ235 treatment resulted in early caspase 3 and 8 activation, 3 hours after the treatment and an activation of caspase 9, 8 hours later.

Histopathological aspects described in patients with chronic hepatitis C.

Chronic hepatitis C affects an estimated 170 million people worldwide and causes approximately 350 000 deaths each year. The current antiviral therapy allows the virus eradication or the permanent inhibition of the virus replication (sustained virological response, SVR), the reduction of the inflammation, and the prevention or the reduction of liver fibrogenesis (histological response). We studied the histopathological aspects found during percutaneous liver biopsy in patients with chronic hepatitis C viral infection who were treated and monitored over a period of two years. The assessment of the histological activity index through Ishak score determined the presence of: mild chronic hepatitis in 12 (23.1%) patients, moderate chronic hepatitis in 21 (40.4%) patients, and severe chronic hepatitis in 19 (36.5%) patients. The percutaneous liver biopsy performed on the patients with chronic viral hepatitis C showed a series of histological alterations, the most frequent being: portal inflammation, periportal necrosis, lobular inflammation, focal necrosis, and hepatic fibrosis (scarring). The severity degree of this histopathological aspect was correlated with the hepatitis activity index. The association of piecemeal with bridging necrosis is the deadline at which the antiviral treatment can still be effective. Evidence of early fibrosis represent the important moment for the antiviral treatment start. The specific histopathological aspects, but not pathognomonic, of chronic hepatitis C (hepatic steatosis, portal lymphoid infiltrates and bile duct damage) had a reduced incidence, occurring in only half (hepatic steatosis), a quarter (portal lymphoid infiltrates) and a fifth (destruction of biliary ducts) of all the patients with chronic viral hepatitis C, and these patterns was correlated with advanced degree of necroinflammatory process of the liver, particularly in the portal tracts.

Effects of therapy with two combinations of antibiotics on the imbalance of MMP-2÷TIMP-2 in chronic periodontitis.

UNLABELLED: Periodontitis represents a chronic bacterial infection that induces immuno-inflammatory conditions affecting gingiva and tooth-supporting tissues. The role of some biological mediators in periodontal disease was widely investigated, especially that of MMP-8 and MMP-9. Recently, MMP-2 was also considered to be an appropriate therapeutic target for prevention of periodontal disease progression. However, effects of the combination of metronidazole with amoxicillin or spiramycin on the release and activation of MMP-2 and the balance MMP-2÷TIMP-2 were rarely studied. This study was designed to assess the influence of two combinations of antibiotics used for treatment of periodontitis on the balance MMP-2÷TIMP-2. Gingival samples obtained from patients with no pharmacological treated chronic periodontitis and those receiving either the association between amoxicillin-metronidazole and spyramicin-metronidazole were processed for paraffin embedding and then used to perform immunohistochemical reactions in order to detect MMP-2 and TIMP-2. All subjects were evaluated clinically and radiographic at the first visit and after treatment completed, the Loe & Silnees gingival index at six sites per tooth for the whole mouth being recorded. Statistical analysis was performed using non-parametrical techniques. Gingiva samples from untreated chronic periodontitis patients revealed a diffuse positive reaction for MMP-2 in the epithelium and also in fibroblasts and macrophages from the lamina propria. For gingiva samples from patients treated with antibiotics, MMP-2 positive reaction was restricted to deep epithelial layers and few cells of the connective tissue. No significant difference was observed for TIMP-2 expression. The clinical indexes were in accordance with immunohistochemical results. After treatment, gingival index values were significantly lower then before (p<0.001) in both groups treated with antibiotics. CONCLUSIONS: The two combinations of antibiotics tested in our study seem to have a dual ability to reduce inflammation as well as to inhibit MMP-2 activity.