Use of Naclof in combined intervention for cataract and glaucoma

Two aspects of using eye drops of a nonsteroid antiinflammatory drug Naclof (sodium diclofenac) are analyzed: maintenance of mydriasis during an intervention (extracapsular cataract extraction with implantation of an intraocular lens and trabeculectomy and arrest of postoperative inflammation. The study was carried out in 40 patients, 20 of which were controls. In the naclof group the diameter of the pupil during the intervention was reliably larger, exudative inflammatory reactions were rarer, and the postoperative vision acuity higher. Hence, naclof is effective in combined interventions for cataract and glaucoma.     

Multivariate analyses of the hominid ulna from Klasies River mouth

BACKGROUND: The combination of 5-fluorouracil (5-FU) and cisplatin has shown great activity in many different types of tumour with an in vitro synergistic effect between 5-FU and cisplatin. A phase II study of 5-FU plus cisplatin was performed in 25 previously untreated patients with inoperable locally advanced or metastatic biliary tract carcinoma. PATIENTS AND METHODS: Twenty-five patients, 10 of them men and 15 women with a median age of 58, were entered into the study. The chemotherapy regimen consisted of 5-FU: 1 g/m2/day in continuous intravenous (i.v.) infusion for five consecutive days, and cisplatin: 100 mg/m2/day on day 2 in a one-hour infusion with standard hyperhydration. Twenty-two patients had metastatic tumours and three had locally advanced disease. RESULTS: Of the 25 patients entered into the study, 24 were evaluable for response and 25 for toxicity. Nausea and vomiting was the main toxic side effect in 19 patients. Severe, WHO grade 3-4 thrombocytopenia or neutropenia were observed in three and seven patients, respectively. There were no toxic deaths. Of 25 patients, six had partial remissions (overall response 24%, 95% confidence interval 7%-41%). For three patients, tumour reduction permitted local radiotherapy and one of these patients with initially advanced disease is still alive six years after the beginning of treatment. CONCLUSIONS: This study, one of the largest phase II trials performed in this disease, shows interesting activity of the combination of 5-FU and cisplatin in advanced biliary tract carcinoma.     

Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide

BACKGROUND: Recruitment of the intracellular tyrosine kinase Syk to activated immune-response receptors is a critical early step in intracellular signaling. In mast cells, Syk specifically associates with doubly phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) that are found within the IgE receptor. The mechanism by which Syk recognizes these motifs is not fully understood. Both Syk SH2 (Src homology 2) domains are required for high-affinity binding to these motifs, but the C-terminal SH2 domain (Syk-C) can function independently and can bind, in isolation, to the tyrosine-phosphorylated IgE receptor in vitro. In order to improve understanding of the cellular function of Syk, we have determined the solution structure of Syk-C complexed with a phosphotyrosine peptide derived from the gamma subunit of the IgE receptor. RESULTS: The Syk-C:peptide structure is compared with liganded structures of both the SH2 domain of Src and the C-terminal SH2 domain of ZAP-70 (the 70 kDa zeta-associated protein). The topologies of these domains are similar, although significant differences occur in the loop regions. In the Syk-C structure, the phosphotyrosine and leucine residues of the peptide ligand interact with pockets on the protein, and the intervening residues are extended. CONCLUSIONS: Syk-C resembles other SH2 domains in its peptide-binding interactions and overall topology, a result that is consistent with its ability to function as an independent SH2 domain in vitro. This result suggests that Syk-C plays a unique role in the intact Syk protein. The determinants of the binding affinity and selectivity of Syk-C may reside in the least-conserved structural elements that comprise the phosphotyrosine- and leucine-binding sites. These structural features can be exploited for the design of Syk-selective SH2 antagonists for the treatment of allergic disorders and asthma.     

Rational polypharmacy in schizophrenia

Approximately 10 to 30% of patients with schizophrenia show poor response to neuroleptics alone. An initial evaluative and treatment approach to these patients is outlined, and the literature on adjunctive treatments, which seek to augment neuroleptic effects, is reviewed. The greatest evidence for efficacy has been shown for lithium, benzodiazepines, carbamazepine, reserpine, and electroconvulsive therapy, although individual patients may also respond to propranolol, clonidine, valproic acid, and L-dopa. Antidepressants may also be useful for treating comorbid depression in nonacutely psychotic patients. One general theme is that no one adjunctive treatment benefits all patients; indeed, only a minority of patients responds to any given agent. Therefore, the choice of specific treatments is best guided by the clinical characteristics of the individual patient. These observations raise the possibility that subgroups of schizophrenia exist; delineation of differences in clinical response to biochemically distinct agents may help elucidate such underlying differences between patient groups.     

In vitro study of the early membrane effects of C27-steroid hormone ecdysterone, immobilized on the nanodispersed magnetite surface]

The object of the study was to reveal the existence of receptor interactions of C27-steroid hormone ecdysterone with the surface of various cells (liver and spleen macrophages, thymus and spleen lymphocytes, erythrocytes and hepatocytes from rat organs) in experiments in vitro using ecdysterone immobilized on the nanodispersed iron surface (which did not penetrate the cell during observation) and the model of fast (during 15 s) activation of phospholipid signal system with ecdysterone. The parameters, which are characteristic of cell phospholipid signal system activation, were evaluated (the concentrations of free arachidonic acid, diene conjugates, tromboxane B2 and leukotriene C4) and its alteration in response to free and immobilized ecdysterone introduction in suspensins of intact cells and cells with the surface modified in vivo by pre-injection of antigen (human erythrocytes). Concurrent binding of immbilized ecdysterone with intact rat cells in the presence of free ecdysterone was also investigated. It was established that there are high-affinity ecdysterone-specific binding sites on the plasma membranes of all cells investigated, Kd estimated according to two different methods varied in the region of 10(-8)-10(-7) M. The characteristic features of the changes in parameters characteristic of phospholipid system activation were revealed to be queite similar in intact cells, as well as in cells with modified surfaces, under introduction of free ecdysterone and immobilized ecdysterone, which did not penetrate into cytosole. The data obtained point to the existence of ecdysterone receptors on the surface of cells plasma membranes and are indicative of the membrane effects as mechanisms of the early pregenomic phase of cells activation by ecdysterone.     

Effects of laser therapy on lipids and antioxidants in blood of patients with bronchial asthma

Laser therapy was assessed for effects on lipoperoxides and free radical catchers in blood lipids of patients with bronchial asthma (BA). When a group of 52 BA patients was compared to healthy donors by dienic conjugates, vitamin E and overall lipid-soluble antioxidants levels in the whole blood and plasma, these appeared higher in the asthmatics. Combination of laser therapy with conventional treatment returned these parameters close to normal.     

L-cystine-di-beta-naphthylamidase activity in plasma of the snake Bothrops jararaca after chronic challenges of water balance

Plasma protein, osmolality and L-cystine-di-beta-naphthylamidase activity were measured in Bothrops jararaca snakes submitted to normal hydration, water deprivation, water loading, salt loading or argvasotocin injections. Protein and osmolality were similar for male and female snakes in all treatments. Protein content was similar in all treatments, indicating the ability of the animals to maintain fluid balance between the vascular and extravascular compartment under osmotic challenges. Osmolality was increased in water-deprived and salt-loaded and was decreased in water-loaded animals compared with normally hydrated or argvasotocin-injected snakes. Enzymatic activity differed between males and females and was higher in salt-loaded females and in arg-vasotocin-injected females and males than in water-loaded snakes. A positive linear regression between osmolality and L-cystine-di-beta-naphthylamidase was obtained for female snakes (correlation coefficient = 0.6162, P < 0.01). The data show a role of arg-vasotocin in the consistent relationship between water balance and this sex-related aminopeptidase activity.     

Frequency of lyme borreliosis and diagnostic titers of antibodies to borrelia burgdorferi in patients with neurological diseases in endemic region of Russia

The frequency of diagnostic titers of antibodies to Borrelia burgdorferi in 289 examinees suffering from neurological diseases made up 10.4%, while in the population this figure was under 1.9%. Lyme-borreliosis was detected in 11 (3.8%) patients, 2 of them had mixed infection with tick-borne viral encephalitis. In 10 patients (3.5%) the diagnosis of neuroborreliosis required verification with other techniques. It is thought valid to perform serological screening for neuroborreliosis only in patients with tick-born encephalitis to identify mixed infection.