Decreased survivability and a DNA repair defect in the cells of patients with xeroderma pigmentosum and Cockayne syndrome under the action of radiation and chemical mutagens

The action of ionizing radiation and chemical mutagens--epoxides (ethylene oxide, propylene oxide, epichlorohydrin)--upon survival and repair processes in xeroderma pigmentosum (XP2SP) and Cockayne syndrome (CS1SP) patients' cells was studied, compared to healthy donor's cells VH-10 and C5RO. Ionizing radiation was demonstrated to enhance significantly higher survival decrease of XP2SP and CS1SP fibroblasts, compared to healthy donor's cells, according to the cloning efficiency criterion. In contrast to this, no significant difference between XP2SP and healthy donor's cells was found, according to cells' ability to replicative DNA synthesis after gamma irradiation. Differences in survival of mutant cells and healthy donor's cells after treatment by epoxides were found significant only following XP2SP being treated by ethylene oxide. DNA single-string breaks in XP2SP and in CS1SP cells treated by mutagens studied were proved to occur with the same frequency as in the DNA of the control cells; however the DNA repair according to this criterion was significantly suppressed in mutant cells.     

Evaluation of acupuncture and occlusal splint therapy in the treatment of temporomandibular joint disorders

One hundred patients showed signs and symptoms of temporomandibular joint disorder, were participated in a one year follow up study. The patients were randomly divided into four groups: Acuhealth treatment (group A), occlusal splint therapy (group B), Acuhealth and occlusal splint therapy (group C), and control (group D). Each group comprised 25 patients. The patients were examined before and 3, 6, and 12 months after treatment. At the three month evaluation, the patients who were not satisfied with the treatment outcome were offered additional treatment. The result showed that 87% of the patients treated by Acuhealth unit, 77.3% of the patients treated with occlusal splint therapy, and 91.3% of the patients received Acuhealth and occlusal splint therapy were improved subjectively and clinically after 3 months follow-up. The patients who responded well to treatment initially also responded well in the long run. The study showed that the Acuhealth unit proved to be an ideal early therapy for TMD, and complemented later with occlusal splint.     

Urinary thromboxane B2 in cardiac transplant patients as a screening method of rejection

Crystallographic studies of a number of aminoacyl-tRNA synthetases and their complexes with ATP, amino acid and cognate tRNA are leading to an increasingly detailed picture of how these sophisticated enzymes function. Within the two distinct structural classes of ten synthetases, many common features are apparent, although evolution has led to many interesting idiosyncrasies in certain enzymes. Recent advances, specifically concerning class II enzymes, have increased our knowledge of both the role of electrophiles in the mechanism of amino acid activation and cross-subunit tRNA recognition and help solve the evolutionary puzzles that have emerged from the extension of the aminoacyl-tRNA synthetase database to include Archae.     

The isolation and analysis of lymphoblastoid cell lines from patients with xeroderma pigmentosum and progeria

Lymphoblastoid cell lines from patients with xeroderma pigmentosum (2 forms) and progeria (unusual form) were established using transformation of peripheral blood lymphocytes by Epstein--Barr virus. The influence of different UV doses on cell vitality, proliferation and cell cycle progression was studied by means of flow cytometry. The cell vitality was determined after incubation of cells with etidium bromide and FDA. We used cytograms with two logarithmic signals (log green/log red) to discriminate the cell cycle status. Cell cultures were used with density of 500,000 cells per 1 ml, previously synchronized at G-phase by the incubation in a medium with low serum content. The effect of UV irradiation was followed during 72 h. Among four analysed cell lines only line XP2SP demonstrated enhanced UV sensitivity, expressed by decreasing of the amount of living cells after the UV dose of 2.5 J/m2 and higher. The cell cycle studies showed that cells were blocked in S-phase and simultaneously the amount of apoptotic cells with both reduced DNA content and ability to bind FDA was seen increased. Similar events were observed in the control line only after the dose of 20 J/m2 and higher.     

The role of positron emission tomography in pharmacokinetic analysis

The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are likely to be particularly useful: (1) In preclinical studies, a new drug can be precisely compared to standard therapies or a series of analogs can be screened for further development on the basis of performance in appropriate animal models. (2) In phase I-II human studies, classic pharmacokinetic measurements can be coupled with imaging measurements (a) to define optimal dosing schedule; (b) to define the potential utility of interventions in particular clinical situations; and (c) to formulate the design of phase III studies that are crucial for drug licensure. In general, the types of measurements that are possible can be grouped into the following categories: 1. In those situations in which the drug can be radiolabeled, the time course of tissue delivery can be determined noninvasively in vivo in health and disease. Such information should be useful for determining dosing schedules, establishing efficacy, and predicting possible toxicity. 2. Ligand-receptor binding can be assessed in vivo in two ways. The ability of the drug to displace standard radiolabeled ligands from their receptors can be determined; alternatively, labeled drug can be used to more directly assess the distribution and time course of binding. These measurements are particularly useful for studying drugs that are active in the central nervous and cardiovascular systems. 3. Measurements of tissue metabolism will be useful in determining the effects of therapies aimed at particular metabolic abnormalities. In addition, these measurements may be useful in defining viability and function of tissues in such widely disparate clinical situations as cancer chemotherapy and cardiology. For example, effects of CNS or cardiovascular drugs can be monitored by observing 18FDG metabolism in brain and heart. We suggest that the joining of classic clinical pharmacology to exquisite imaging measurements will help form the basis for 21st-century clinical drug development.     

Gastric erosions induced by nonsteroidal anti-inflammatory drugs: clinical significance, pathogenesis, and therapeutic perspectives

The development of ulceration and ulcer complications by nonsteroidal anti-inflammatory drugs (NSAIDs) is now well established. Gastric erosions occur in about 60% of patients receiving long-term NSAID therapy. Many clinicians consider such erosions benign in nature and not requiring therapeutic intervention. Recent evidence, however, indicates that gastric erosions predispose rheumatic patients to frank ulcerations and ulcer complications. This brief overview summarizes the clinical dilemma in the diagnosis and treatment of NSAID-induced gastric erosions. Current data suggest that misoprostol has important therapeutic benefits for the treatment and prevention of gastric erosions in patients receiving long-term NSAID therapy.     

Two antipeptide monoclonal antibodies that recognize adhesive sequences in fibrinogen: identification of antigenic determinants and unrelated sequences using synthetic combinatorial libraries

Fulminant hepatic failure is infrequently seen as a consequence of acute congestive heart failure. Recognition of this entity is important as treatment directed towards heart failure should help resolve the liver failure. A case of fulminant hepatic failure due to previously unrecognized cardiomyopathy is presented. A liver transplantation was being considered for fulminant hepatic failure until hemodynamic monitoring studies demonstrated that, in fact, the patient had severe cardiomyopathy. Treatment directed at his cardiomyopathy resolved the liver failure. Therefore, prompt recognition of such a phenomenon would enable early institution of appropriate therapeutic measures with the hope of clinical benefit to the patient.     

Synthesis and anticonvulsant activity of new thiazolidinone and thioxoimidazolidinone derivatives derived from furochromones

Various new thiazolidinone and thioxoimidazolidinone derivatives were synthesized starting from 4,9-dimethoxy-5 H-furo[3,2-g][1]benzopyran-5-on-7-carboxaldehyde. The anticonvulsant activity of the synthesized compounds was evaluated. Most of the compounds showed anticonvulsant activity equal or superior to phenobarbital.