Specific increase of L-dopa levels in plasma upon infusion of tyrosinase containing liposomes

1. The present paper reports the effects of liposome-entrapped tyrosinase (EC 1.14.18.1. L-Tyrosine, L-3,4-dihydroxyphenylalanine: oxygen oxidoreductase) infusion on the catecholamine contents of rat plasma. The actions of liposomes and free tyrosinase have also been investigated. 2. From the experiments, evidence has been obtained that liposome-entrapped tyrosinase is able to affect specifically L-3,4-dihydroxyphenylalanine (L-DOPA) levels which increase dramatically. 3. The possible use of liposome-entrapped tyrosinase to raise L-DOPA levels in catecholamine related disorders is discussed. 4. Liposomes without tyrosinase provoke no significant changes of catecholamine or L-DOPA levels while free tyrosinase does induce a change but in a less constant fashion than the liposome-entrapped enzyme.     

Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 micrograms/24 hours: a pilot study

The pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24 h were studied in a group of 12 normally menstruating women during 90 days of continuous use (i.e., during three 30-day treatment segments). Blood samples were drawn immediately before insertion, 15 and 30 min, as well as 1, 2, 4, 8, 12 and 24 h after insertion of the rings, and thereafter three times weekly throughout the study for the analysis of L-NOG, estradiol, progesterone and sex hormone-binding globulin (SHBG). Endometrial biopsies were obtained for a morphometric analysis in a pre-treatment (control) cycle and in the 6th and 10th weeks of treatment. The peak of average L-NOG levels was reached within two hours after the insertion of rings. Until 24 h after insertion, the levels did not change significantly. Thereafter, a decrease at a rate of 0.2% per day was initiated. The L-NOG and SHBG levels were highly correlated. This was seen for both the pre-treatment SHBG vs L-NOG (r = 0.96) and the treatment SHBG vs L-NOG levels (r = 0.92). There was a significant (p < 0.001) decrease of SHBG levels due to treatment. During the total of 36 treatment segments, a normal ovarian function was seen in 47% of the segments. The women were anovulatory and had an inadequate lutal function in 28% and 25% of segments, respectively. No correlation between the L-NOG levels and ovarian reaction to treatment was found. The use of L-NOG induced significant changes in the endometrium; the number of glands/mm2 decreased after 6 (p < 0.02) and 10 weeks of use (p < 0.01). Also, the diameter of glands and the occurrence of vacuolated cells decreased significantly (p < 0.02 and p < 0.005, respectively). None of the endometrial parameters or dating was correlated with the ovarian reaction to treatment, indicating independent endometrial effects of L-NOG.     

The risk of seroconversion in surgeons of the hepatitis B, hepatitis C and human immunodeficiency viruses (in a specific surgical population)

The prevalence of hepatitis B surface antigen (HBs Ag) and antibody to hepatitis C virus (HCV) and human immunodeficiency virus (HIV) was determined in the serum specimens of 288 patients treated surgically in the orthopaedic department of an urban public teaching hospital. The cumulative risk of HBV, HCV and HIV seroconversion for an orthopaedic surgeon during the surgical career span was calculated. We found that 1.4%, 3.1% and 1.7% of patients were seropositive for HBsAg, HCV antibody and HIV antibody, respectively. Seropositivity was neither associated with age nor with trauma, whereas male patients had a greater likelihood of seropositivity. Risk factor assessment did not prove to be discriminating in identifying which patients may pose a potential exposure risk. This study supports the concept of universal infection control precautions for orthopaedic surgeons regardless of the patients' risk factor or serologic status.     

Invasion of hereditary ovalocytes by Plasmodium falciparum in vitro and its relation to intracellular ATP concentration

Hereditary ovalocytes (stomatocytic ovalocytes), when examined within 1-2 days from the time that the blood sample is drawn, are invaded by Plasmodium falciparum in culture to the extent of at least 55% of normal control cells. The ovalocytes have extremely rigid membranes, characterised by a shear elastic modulus some 3-4 times greater than that of normal cells. The extent of invasion falls off very much more rapidly than that into normal cells on storage, and we surmise that this is the reason for earlier reports of resistance of ovalocytes to malarial invasion in vitro. The initial loss of susceptibility to invasion with time is not accompanied by any change in membrane rigidity, but is primarily a consequence of a rapid decline in intracellular ATP concentration: this falls to below the threshold level required for invasion (approx. 0.1 mM) over a period in which the ATP in normal cells remains almost constant. Incubation in a metabolic regenerating medium leads to a rise in the intracellular ATP concentration and invasion by P. falciparum is recovered, though to a much lower extent than in normal cells. The resistance of ovalocytes to invasion becomes irreversible, due possibly to degradative processes in the membrane, on further storage. The developing parasites in ovalocytes have a reduced number of merozoites and show distinct morphological abnormalities.     

Bloom syndrome cells undergo p53-dependent apoptosis and delayed assembly of BRCA1 and NBS1 repair complexes at stalled replication forks

Bloom syndrome (BS) is a hereditary disorder characterized by pre- and postnatal growth retardation, genomic instability, and cancer. BLM, the gene defective in BS, encodes a DNA helicase thought to participate in genomic maintenance. We show that BS human fibroblasts undergo extensive apoptosis after DNA damage specifically when DNA replication forks are stalled. Damage during S, but not G1, caused BLM to rapidly form foci with gammaH2AX at replication forks that develop DNA breaks. These BLM foci recruited BRCA1 and NBS1. Damaged BS cells formed BRCA1/NBS1 foci with markedly delayed kinetics. Helicase-defective BLM showed dominant-negative activity with respect to apoptosis, but not BRCA1/NBS1 recruitment, suggesting catalytic and structural roles for BLM. Strikingly, inactivation of p53 prevented the death of damaged BS cells and delayed recruitment of BRCA1/NBS1. These findings suggest that BLM is an early responder to damaged replication forks. Moreover, p53 eliminates cells that rapidly assemble BRCA1/NBS1 without BLM, suggesting that BLM is essential for timely BRCA1/NBS1 function.     

New Meaning to it Alignment

One of the perennial top issues in surveys of IT management concerns is IT alignment. It always seems to be in the top-ten, but cyclically rises to number-one at times of economic decline. When the economy turns down, information services departments are called upon to redouble their vigilance on spending and to focus their attention on projects and initiatives that are in line with the near-term objectives of the overall business. the enterprises that have developed collaborative management processes between the business and information services organizations do this best and with the least amount of disruption. in fact, it seems that there has been tremendous progress in the past ten or fifteen years in terms of leadership and management practices on the part of both business and information services organizations that have contributed to a dramatic improvement in the handling of downward economic adjustments. Upward economic change, on the other hand, poses more perplexing challenges.