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The serum concentration of Zn and Cu were determined in 126 controls and 160 patients-with atherosclerosis obliterans (AO) and 53 patients with thromboangiitis abliterans (TO). The concentration of serum Zn decreases with age both in controls and patients with AO in all the evolutive stages of the disease. In patients with TO, the concentration of serum Zn shows no correlation with age. The significantly lower values of serum Zn in controls and patients with AO over 61 yr than those below this age is attributed to the decreased Zn supply, especially to some individual cellular abnormalities. The values of serum Cu are higher in patients with AO and TO than in controls irrespective of the evolutive stage of the disease. This was related to cigaret smoking and inflammation. The Zn/Cu ratio in the serum is below 1 in patients with AO and TO and in controls over 61-yr-old. The pathogenetic role of this ratio in atherosclerosis and inflammation still remains a controversial question. [ABSTRACT FROM AUTHOR]

A quantitative ELISA using monoclonal and polyclonal antibodies against neoantigens of the terminal C5b-9 complement complex was used to evaluate the presence of terminal complexes in 68 human arterial samples with or without atherosclerotic involvement. Plasma levels of SC5b-9 were directly compared with the corresponding levels eluted from the femoral arteries in six patients undergoing surgical procedures. The plasma concentration of SC5b-9 in these donors was in the range of 30-90 arbitrary units (AU)/ml, equivalent to 100-300 ng/ml SC5b-9 or 45-130 AU/100 mg plasma protein. All the arterial samples contained detectable amounts of C5b-9. The aortic normal and fatty streaks intimae presented a minimum mean value of 65 ± 12 AU/100 mg total protein, in the range of normal plasma SC5b-9 levels. The corresponding media contained significantly higher amounts of terminal complexes (115 ± 30 AU/100 mg protein). Markedly increased levels of C5b-9 were eluted from aortic intimal thickenings (350 ± 100 AU/100 mg protein) and the corresponding media (300 ± 53 AU/100 mg protein). Similar concentrations were found in aortic fibrous plaques (340 ± 80 AU/100 mg protein). The observed correlation between C5b-9 levels and atherosclerotic alterations in arterial walls is suggestive of chronic complement activation with involvement of the terminal complement sequence at these sites. These processes may contribute to progression of the arteriosclerotic lesions. [ABSTRACT FROM AUTHOR]

Introduction: In trials investigating antidepressants, placebo response averages 31% compared to a mean medication response of 50%, and the difference is even smaller in clinical studies with children and adolescents, which represents a major obstacle in detection of an efficacy signal. Objectives: To find the main factors involved in the augmentation of placebo response in clinical trials with antidepressants, and to find ways to reduce this response. Methods: A literature review was performed using as paradigm "placebo effect" or "placebo response" and "antidepressants" and "clinical trials". All papers published between 2000 and 2019, found in the main electronic databases (EMBASE, CINAHL, PubMed, Cochrane), were included in the primary review. Results: Expectancy-based placebo effects, statistical procedures, motivation for participation in trials, frequency of study visits and their length, frequency of drugs administration are all related to the rate of placebo response. The trial design should attempt to control as many of these factors as possible, e.g. single-blind lead-in periods which have the purpose to identify and exclude participants with quick response to placebo, decreasing the length of study visits and the number of interactions between subjects and investigators, training the investigator to minimize their placebo-enforcing effects, all these may yreduce the amplitude of the placebo response. Conclusions: The design of the clinical trials in major depression patients should try to control placebo-increasing factors related to the subjects, environment, investigators, statistical procedures, and investigational products, in order to allow the effect of an antidepressant to be differentiated from placebo. [ABSTRACT FROM AUTHOR]

Introduction: High levels of pro-inflammatory markers (e.g. TNFalfa, IL-6, C-reactive protein) have been reported in patients diagnosed with major depressive disorder (MDD). Inflammation has been considered a potential factor that may worsen the MDD evolution, therefore drugs that interfere with inflammatory processes have been suggested as add-on to antidepressant therapy in partial or resistant cases. Objectives: To evaluate the current data in favour of recommendation for anti-inflammatory drugs as augmentation agents in the treatment of MDD. Methods: A literature review was conducted in the main electronic databases (PubMed, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Thomson Reuters/Web of Science) using the search paradigm "anti-inflammatory drugs" OR "immune modulators" AND "major depressive disorder". All papers published between 1990 and 2019 were included in the primary analysis, than they were filtered by using pre-determined inclusion and exclusion criteria. Results: Infliximab is an anti-TNFa chimeric monoclonal antibody that decreased depression severity in patients with an increased initial level of inflammation markers in clinical trials. Adalimumab is a monoclonal antibody with anti-TNFa properties that decreased the severity of depressive symptoms after 12 weeks in patients with psoriazis, while etanercept (also an anti-TNFa inhibitor) confirmed its efficacy over the affective symptoms during an 84 weekextension trial in patients with the same dermatological pathology. Tocilizumab and sirukumab are studied as add-on to antidepressant drugs, but the results are still inconclusive. Conclusions: Although immune modulation therapy is a new type of intervention for MDD, it may be a promising intervention for MDD with partial response to antidepressants. Disclosure: First author was speaker for Astra Zeneca, BristolMyers Squibb, CSC Pharmaceuticals, Eli Lilly, Janssen Cilag, Lundbeck, Organon, Pfizer, Servier, Sanofi Aventis, and participated in clinical research funded by Janssen Cilag, Astra Zeneca, Eli Lilly, San. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of non pharmacological primary prevention of hypertension., Methods: Analysis of all the available trials with a minimal one-year follow-up and one recently study with 8 weeks follow-up. The outcomes consisted in blood pressure changes and incidence of hypertension at the end of the study., Results: Five reviewed randomized controlled trials with a minimal one year follow-up and one recently study with eight weeks follow-up assessed the following intervention: advice about sodium restriction, weight reduction, physical exercise and relaxation, a diet rich in fruits vegetables and low fat dairy foods. All the results were available according to the "intention to treat principle". The feasibility appeared to be initially good, but decreased with time, confirming the difficulty of long term prevention. The prevention effect was mild with a decrease in hypertension incidence of a few percent (2%) and blood pressure decrease of only a few mmHg reduction (mean of 3 mmHg). Three community studies were reviewed. The prevention interventions were carried out on entire populations. The feasibility was bad (great number of lost-follow-up). The results on the blood pressure incidence were available in only one study and the blood pressure decrease estimates were heterogeneous, so the results cannot be generalized., Conclusion: The primary prevention of hypertension shows disappointing results when the intervention duration is above one year. It leaves little hope for a significant effect on blood pressure dependent cardiovascular events.

The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S-protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of breast cancer and on 6 samples of benign breast tumors using polyclonal or monoclonal antibodies and the streptavidin-biotin-peroxidase technique. All the tissue samples with carcinoma in each the TNM stages presented C5b-9 deposits on the membranes of tumor cells, thin granules on cell remnants, and diffuse deposits in the necrotic areas. When chemotherapy and radiation therapy preceded surgery, C5b-9 deposits were more intense and extended. The C5b-9 deposits were absent in all the samples with benign lesions. S-protein/vitronectin was present as fibrillar deposits in the connective tissue matrix and as diffuse deposits around the tumor cells, less intense and extended than fibronectin. IgG, C3, and C4 deposits were present only in carcinoma samples. The presence of C5b-9 deposits is indicative of complement activation and its subsequent pathogenetic effects in breast cancer.

The study included 62 patients with atherosclerosis obliterans of the lower extremities, of whom 47 in stage II, 5 in stage III and 10 in stage IV of the disease. In 22 patients were present single arterial obliteration, in 30 patients multiple, layered arterial obliterations, in 8 distal arterial obliterations and 2 a diffuse atherosclerosis of the lower extremities. Patients were examined in admission to the clinic, after the treatment performed at the clinic and at various intervals, during 2-4 years. The segmental arterial pressure, the pressure index and the ultrasonogram recorded with the Cardior electrocardiograph were followed-up. The arterial pressure and the pressure indices returned to normal values only after invasive procedures. The medical treatment can bring about the clinical regression and stabilization of the disease, as well as the improvement of the ultrasonogram. For the choice of therapeutic means, the pressure index is the best criterion, since it correlates with the severity of the disease. In the case of a pressure index 0.75, the medical treatment or the transluminal dilatation is preferred, whereas at an index of 0.7 the surgical revascularisation is considered necessary. Other ultrasonic parameters were also taken into account, such as the systolic passage time and the maximum velocity, which are less important in the attainment of the mentioned aims.(ABSTRACT TRUNCATED AT 250 WORDS)

The co-localization of terminal C5b-9 complement complexes and macrophages was investigated in human arteries with atherosclerosis using a double-labeling immunohistochemical technique. Macrophages were found in all the atherosclerotic arteries, with the accumulation correlating positively with the degree of atherosclerosis. This accumulation was associated with an increase of C5b-9 deposits, as well as with an increase in the number of deposits containing both complement components and macrophages ('co-localization'). This co-localization was found to pertain both to intact macrophages and to macrophage remnants. These data suggest that C5b-9 complement complex might be formed on macrophages with subsequent promotion of inflammatory events and progression of the atherosclerotic lesions.

The absolute and relative bioavailability of nifedipine (1) from different formulations administered as single oral doses in healthy volunteers was determined. Serum concentrations of 1 were measured by GC. The absolute bioavailability of 1 was 53% because of presystemic metabolism. The bioavailability of Adalat (Bayer) tablets, Nifedipina (Terapia) and Corinfar (VEB Arzneimittelwerk Dresden) sugar-coated tablets was 93%, 92% and 86% (respectively) as compared with Adalat capsules. The AUC were not significantly different. The Cmax and tmax values were different, indicating that the absorption of 1 showed differences in first-order rate constants of dissolution in the above mentioned order. Despite the differences among the formulations studied, each preparation may have its merits. In a multiple dose regimen of 20 mg 1 (Nifedipina, Terapia) t.i.d., minimal therapeutic drug levels were achieved and maintained during steady state, from the 1st d of treatment.

Gamma-glutamyltransferase (gamma-GT) was found to exceed the upper normal limit in 31 of the 32 patients with liver metastases verified during surgery or at autopsy, while the level of this enzyme was normal in 25 of the 28 patients with proven neoplasma but without evidence of metastatic involvement of the liver. Particularly high values of gamma-GT activity were noted in 9 patients in whom liver metastases were accompanied by clinical jaundice. A similar behaviour was noted for alkaline phosphatase but changes affecting this enzyme were less obvious. Thus, for a mean increase of gamma-GT to levels up to seven times the upper normal limit, the level of alkaline phosphatase increased only three times. A decrease of serum pseudocholinesterase occurred in most patients with neoplasma, the process being more evident when liver metastases were present. It is concluded that an increase of gamma-GT in a patient with neoplasma could be considered as a marker of hepatic metastases, if chronic alcoholism or hepatobiliary disease can be excluded.

Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency.

Serum concentration of ionic calcium and the effect of dietary salt restriction on serum total calcium was studied in patients with essential arterial hypertension. The concentration of serum ionic calcium was significantly lower than in controls in all the evolutive stages of the disease (p less than 0.005; p less than 0.005; p less than 0.001). During salt restriction serum total calcium rises significantly (p less than 0.005) as compared with the values found under a salt containing diet. It was suggested that increased chronic ingestion of sodium or restriction of dietary salt produces alterations in Na-Ca exchanges across semipermeable membrane of the smooth muscle.