Effect of divalent cations on structure-function relationships of the antitumor protein α-sarcin

α-Sarcin binds one Zn(II) cation per protein molecule, with a K_d value of 0.9 mM, determined by equilibrium dialysis experiments. Ca(II), Mg(II), and Mn(II) do not bind to α-sarcin. Cd(II) and Co(II) also behave as Zn(II). The binding produces local modifications on the protein conformation affecting the microenvironment of tryptophan residues. The three cations modify the fluorescence emission of the protein. The near-u. v. circular dichroism spectrum of the protein is also altered. The binding of Zn(II) and related cations does not modify the secondary structure of the protein. The ribonucleolytic activity of a-sarcin is inhibited upon Zn(II) binding, but no alteration of the ability of the protein to aggregate phospholipid vesicles has been observed.     

Optimized Photodynamic Therapy with Systemic Photosensitizer Following Debulking Technique for Nonmelanoma Skin Cancers

BACKGROUND: The thickness and depth of invasion of skin tumors may be limiting factors for topical photosensitizer-based photodynamic therapy (PDT). The use of PDT with systemic photosensitizer needs to be further explored as a modality of treatment for nonmelanoma skin cancer (NMSC). OBJECTIVE: The objective was to present six patients with multiple, nodular, and/or pigmented NMSC treated successfully with purified hematoporphyrin derivative (PHD) and PDT using prior debulking. METHODS: After 24 hours of systemic PHD (1.5 mg/kg), 12 lesions of NMSC were selected for PHD-PDT alone and 6 nodular/elevated lesions for PHD-PDT following a debulking procedure. The tumor area was illuminated in one single-dose session of 300 J/cm(2), at an intensity range of 130 to 150 mW/cm(2), with a 630-nm-wavelength diode laser. RESULTS: The prior curettage provided significant reduction in volume and/or pigmentation of lesions. After the session of PHD-PDT with prior curettage and additional topical 20% ALA-PDT in two lesions or PHD-PDT alone, 83% (5/6) of lesions and 58% (7/12) of lesions, respectively, maintained a complete clinical response, 22.2+/-8.9 months of follow-up. CONCLUSIONS: The combination of prior debulking with systemic agents-PDT appears to be a good option for multiple, pigmented, and/or nodular lesions of NMSC and can allow the improvement of clinical results.     

Risk Factors in the Use of Benzodiazepines

Gené-Badia J, Blay-Pueyo C and Soler-Vila M. Risk factorsin the use of benzodiazepines. Family Practice 1988; 5: 283–288. A case-control study was carried out on 107 benzodiazepine usersand 214 controls not treated with anxiolytic-hypnotic agents,chosen randomly and matched two to one for each case by age,sex and family doctor. The users presented a higher degree ofpsychic disorder than the controls, with depression, interpersonalsensitivity, and the total number of symptoms being the elementsdistinguishing the two groups. We have found two factors thatput the population at large at risk for using benzodiazepines;the family doctor's diagnosis of a mental disorder in the clinicalhistory and the daily use of drugs other than benzodiazepinesexplained the risk independently. The presence of chronic disorders,especially cardiological and musculoskeletal disorders, alsoshowed a significant risk, but were only explained by theirclose association with one of the first two factors. It is postulatedthat general practitioners, who are the principal prescribersof drugs, are causing over-medication in the population.     

A New Acceleration Driven Pacemaker: Rate Modulation Versus Normal Sinus Rhythm—Comparison During Treadmill Exercise

The pocing rate response of a new acceleration driven pulse generator (SWING 100, SORIN BIOMEDICA) was compared with simultaneous normal sinus rhythm (NSR) during two different treadmill exercises. This pacemaker has a gravitational acceleration sensor able to discriminate between physical activities and vibrations. Six healthy volunteers (three male, three female; aged 21.7 ± 4,3 years), with the pacemaker strapped to their right infraclavicular area, performed each test three times with different rise response curve (RRC) each time: fast, normal, and slow. The fall response curve used was the same as the rising one during each test. Pacing rates were recorded using the VEGA analyzer (SORIN BIOMEDICA) and compared with simultaneous NSR recorded by a 7-channel ECG recorder (MINGOGRAF 7, SIEMENS), During all tests immediate (within seconds) rapid increase in pacemaker rate was seen up to about 60 seconds, then a slower increase followed thereafter. The mean correlation between pacing rates and NSR during the Bruce tests were 0.7941 ± 0.10, 0.8562 ± 0.14, and 0.8292 ± 0.07; during the discontinous tests 0.7292 ± 0.16, 0.7233 ± 0.10, and 0.7480 ± 0.11 for fast, normal, and slow RRC, respectively. Each 30 seconds, nonsignificant differences were present between pacing rate and NSR during all the discontinuous tests; similar responses were observed only during the first two stages of Bruce tests after which NSR was significantly higher than pacemaker rates. The speed of rise to upper rate was the main difference between the different programs (fast, normal, and slow). The discontinuous tests showed that the pacemaker responds more to speed than to grade. In conclusion, the Swing pacemaker is easy to use and program, fast, reliable, and is able to mimic the normal sinus behavior especially during discontinuous activities.     

ACETALDEHYDE METABOLISM: DIFFERENCES BETWEEN UChA AND UChB RATS

In order to explore the influence of acetaldehyde (AcH) metabolismon the voluntary ethanol intake of genetically low (UChA) andhigh (UChB) ethanol consumer rats, the AcH disappearance rate(ADR) after incubation with homogenates and subcellular fractionsfrom liver and brain was determined. In addition, the effectof disulfiram pretreatment on AcH metabolism was studied. Maleadult rats of both strains were used. ADR was assayed in totalhomogenates, and in mitochondrial as well as 9000 g supernatantfractions of liver and brain. AcH was measured by gas chromatography.In some experiments, rats were pretreated with disulfiram (300mg/kg po) 24 hr before the studies. The result showed no straindifference in ADR in homogenates or subcellular fractions ofliver from untreated rats, but for disulfiram pretreated ratsa significantly lower decrease of ADR in samples from UChB comparedto UChA rats was observed. This result is consistent with alower peak AcH level in UChB compared to UChA rats after a loadof ethanol (60 mmole/kg ip). Concerning brain homogenates, ahigher ADR was observed in homogenates and crude mitochondrialfractions of UChB than of UChA rats. This difference was notobserved when the incubation was performed without adding NADor in the absence of oxygen. These results provide evidenceof strain differences in mitochondrial AcH metabolism, the natureand origin of which deserve further study.     

ETHANOL DECREASES BASAL CYTOSOLIC-FREE CALCIUM CONCENTRATION IN CULTURED SKELETAL MUSCLE CELLS

We analysed the effect of ethanol on basal cytosolic-free calciumconcentration ([Ca²⁺]₁) in cultured rat myocytes. Ethanol causeda dose-dependent decrease of the resting [Ca²⁺]₁). Removal ofethanol was followed by a transitory increase of [Ca²⁺]₁ abovethe basal level. In cells chronically exposed to ethanol, [Ca²⁺]₁normalized to the previous level.     

The cold pressor test: Vascular and myocardial response patterns and their stability

The purposes of the present study were to compare the cardiovascular response patterns evoked by three versions of the cold pressor test (either forehead stimulation or hand or foot immersion) and to determine the reproducibility of the responses over a 2-week interval. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, and systolic time intervals were obtained during rest and during the cold pressor test in 42 young men. Across conditions, the pressor response was supported by peripheral resistance increases with concomitant stroke volume decreases. Although the response panerns were generally similar across sites, exceptions were apparent for heart rate. Forehead stimulation was characterized by no significant change in heart rate, whereas limb (hand or foot) immersion was associated with significant heart rate acceleration. The responses elicited by the three cold pressor test conditions were reliable and showed little evidence of attenuation over the test-retest interval.     

Smooth muscle myosin light chain kinase is transiently expressed in skeletal muscle during embryogenesis and muscle regeneration both in vivo and in vitro

Byusing a polyclonal antibody raised against smooth muscle MyosinLight Chain Kinase of adult chicken we show that the 135 kDasmooth muscle Myosin Light Chain Kinase isoform is present inneonatal and regenerating rat skeletal muscle, as well as inadult atrial myocardium. No reaction was evident in adultskeletal muscle fibres. In neonatal and in early regeneratingmuscle smooth muscle Myosin Light Chain Kinase is associated withembryonic myosin as revealed by their co-presence in musclefibres. Experiments in vitro show the same results in myotubes.In atrial myocardium there is a patchy positivity in certaingroup of myocytes. Immunoblotting experiments show in muscle cellcultures, in neonatal and in regenerating skeletal muscle aprotein band with electrophoretic mobility corresponding to thatof smooth muscle Myosin Light Chain Kinase. These results suggestthat the expression of smooth muscle Myosin Light Chain Kinase isnot fully tissue-specific and that regulation of the contractilemachinery could be different during myogenesis and in adulthood,in relation to the peculiar dynamic characteristics of developingmuscles