Comorbidity of drug dependence and other mental disorders: a two-phase study of prevalence at outpatient treatment centres in Italy

The proposed mechanism of action of the antineoplastic drug 3-nitrobenzothiazolo[3,2-alpha]quinolinium chloride (NBQ-2) involves its interaction with DNA by intercalation and inhibition of topoisomerase II activity by arresting the enzyme in a covalent cleavage complex. In an attempt to identify some structural determinants for activity and develop a molecular structure/cytotoxicity correlation, four new structural analogs of the antitumor NBQ-2 were prepared and their cytotoxic activity and DNA binding properties were investigated. The cytotoxic activity was evaluated against six different human tumor cell lines: U937, K-562, HL-60, HT-29, HeLa, and A431. The results showed that these new drugs elicit pronounced cytotoxic effects against U937, K-562, HL-60 and A431 while HeLa and HT-29 were less sensitive to the new drugs. This apparent selectivity was different to that of m-AMSA, a drug currently used for cancer treatment. Since the interaction of NBQ-2 to DNA by intercalation has been proposed as the initial step leading to its antineoplastic activity, DNA binding and changes in DNA contour length induced by the new NBQ-2 structural analogs were also investigated using calf thymus and human DNA. The drug, 7-(1-propenyl)-3-nitrobenzimidazolo[3,2-alpha]quinolinium chloride (NBQ-59) was the most cytotoxic agent of the analog series (IC50 = 16 microM for HL-60 cells), however, it demonstrated the weakest binding to DNA (Kint = 0.9 x 10[5] M-1 for calf thymus DNA). NBQ-59 was also found to be a poor intercalator into the DNA double helix. Therefore, our results suggest that DNA binding is not the primary mechanism of drug action for this family of compounds. In addition structural determinants important for cytotoxicity of the benzazolo quinolinium chlorides were suggested by our results. In particular, the nitro group in the 3 position does not seem to be necessary for bioactivity, while substitutions in the benzazolo moiety have striking effects on the biological activity of the drugs.     

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.     

Computerized determination of proliferating cell nuclear antigen expression in meningiomas. A comparison with non-automated method

Proliferating cell nuclear antigen (PCNA) expression has been proven to be a significant marker of cell proliferation in meningiomas, which correlates with growth rate and, as shown by several authors, possibly provides prognostic information concerning biologic behavior. However, the current method for determining PCNA labeling index (LI) is tedious and time consuming like all the nonautomated methods for evaluating cell kinetics, presenting high interobserver and interlaboratory variability and low reproducibility. In the present study, we introduce a semi-automated computer-assisted image analysis method for determining PCNA LI in 38 meningiomas, in parallel with the current nonautomated method. Image analysis technique permits unbiased cell counting, standardizes the degree of staining intensity and provides instant results. By calculating coefficient of variability, the method proved to be highly reproducible. The correlation between the results provided by the nonautomated and the semiautomated image analysis method showed a high agreement between them, with a correlation coefficient, r, of 0.82. In conclusion, we consider that image analysis contributes to the accuracy, reproducibility, and practicality of PCNA LI determination so that along with other useful parameters this significant marker may serve to predict the clinical behavior in meningiomas.     

Synchronisation of hyperchaotic oscillators

The authors present three different examples demonstrating the possibility of synchronising hyperchaotic oscillators via a single variable     

A new actigraph for long-term registration of the duration andintensity of tremor and movement

Actigraphy, the long-term measurement of human movement with a small solid state recorder, is gaining acceptance as a useful method in many research fields. Currently available actigraphs assess or estimate the movement duration per time interval. However, the output gives no information on movement type or intensity, and cannot be used in subjects suffering from tremor. The present paper describes a new type of actigraph, that has been developed primarily for the long-term evaluation of motor symptoms in Parkinson patients. The device is the first to discriminate tremor from other movements and to assess both duration and intensity of the two types of movement. It is based on a Motorola 68HC805B6 microcontroller and contains: an accelerometer, programmable gain stages, programmable low- and highpass filters, a programmable level comparator, a peak detector, interface circuits, a real time clock, data storage, and control circuitry. The micro-controller performs a period amplitude sequence analysis (PASA) on the conditioned accelerometer signal, and stores four output variables (tremor duration, tremor amplitude, movement duration, and movement amplitude) at the end of programmable time intervals. The analysis of fluctuations in the motor symptoms of, e.g., Parkinson patients using this actigraph can be of great help in the pharmacological management of symptoms     

Noise contribution of the body resistance in partially-depleted SOIMOSFETs

An additional noise component is observed in the noise spectrum of transistors in a partially-depleted (PD) medium-thickness SOI-CMOS technology. We identify the origin of this additional noise in the noisy resistance of the body film. This resistance, coupled to the gate capacitance, forms an RC filter and generates the hump-shape of the additional noise component. Several experimental observations that support this model are presented     

Nonlinear conductivity and current-voltage characteristics of two-dimensional semiconductor superlattices

Electron transport and heating in a two-dimensional semiconductor superlattice with arbitrary orientation of the field (current) relative to the crystallographic axes is investigated in the approximation of constant energy and velocity relaxation times with electron-electron collisions taken into account. The nonlinear conductivity, average electron energies, and interrelationship between field direction and the current excited by it in an unbounded superlattice, as well as the current-voltage characteristics and the transverse electromotive force of a superlattice of finite width are found. Fiz. Tekh. Poluprovodn. 31, 308–310 (March 1997)     

Application of gene gun for local-regional cancer

We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.