Synthesis and cardiovascular activity of new 8-alkylamino-1,3-dimethyl-7-(2-hydroxy-3- piperazinopropyl)-3,7-dihydro-1H-purine-2,6-diones

7-{2-Hydroxy-3-[4-(2-phenoxyethyl)-piperazinyl-1-yl]-propyl}-1,3-di-methyl-3,7-dihydro-1H-purine-2,6-dione dihydrochloride (2), and several of its 8-alkylamino substituted derivatives (11-17) were synthesized and tested for electrocardiographic, antiarrhythmic and hypotensive activity. Also their alpha(1)- and alpha(2)-adrenoreceptor affinities were determined. It was found that compound 2, and its analogue 15 with 8-(2-morpholin-4-yl-ethylamino) substituent displayed a strong prophylactic antiarrhythmic activity in experimentally induced arrhythmia (LD50/ED50 = 54.9 and 55.0, respectively). The hypotensive activity was observed for 8-benzylamino (11) or 8-(pyridin-2-yl-methylamino) (12) analogues. All the new derivatives (11-17) and 2 showed a weak affinity for alpha1-(Ki = 0.225-1.400 microM) and alpha2-(Ki = 0.152-4.299 microM) receptors.     

Calcium channel antagonists attenuate cross-sensitization to the locomotor effects of nicotine and ethanol in mice

The present study was focused on evaluation of locomotor cross-sensitization between nicotine and ethanol in mice. First, we demonstrated that, after 5 daily injections, nicotine (0.5 mg/kg, ip) produced sensitization to its own locomotor stimulant effect. Moreover, nicotine-experienced mice manifested an enhanced response to ethanol challenge (2 g/kg, ip) indicating the development of cross-sensitization between nicotine and ethanol in mice. Additionally, the L-type voltage-dependent calcium channel antagonists: verapamil and diltiazem, but not nimodipine, at the dose of 20 mg/kg, injected before the ethanol challenge, blocked the expression of this cross-sensitization. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in the sensitization to locomotor stimulant effects of nicotine and ethanol and point to certain differences in acute behavioral effects of various classes of calcium channel inhibitors.     

Loss of heterozygosity at chromosomes 3p and 17p in primary non-small cell lung cancer

BACKGROUND: Loss of heterozygosity (LOH) of selected regions at chromosomes 3p and 17p in non-small cell lung cancer (NSCLC) and the association of these abnormalities with major clinical parameters and prognosis were studied. MATERIALS AND METHODS: The study group included 92 consecutive primary NSCLC tumours and four microsatellite markers from chromosome 3p and three markers from 17p were analyzed. RESULTS: LOH of at least one locus was found in 83% of all analyzed tumours. Most frequently deletion (58%) was found at locus D3S1481 (3p14.2). Sequence deletions of D17S520 (17p12) and TP53 (17p13.1) occurred in 52% of tumours. LOH occurrence at 3p and 17p was more frequent in squamous cell carcinomas compared to adenocarcinomas (89% vs. 75%), but this difference was not significant. CONCLUSION: No significant association was found between LOH on any analyzed loci and tumour stage (TNM) and grade (G). There was no correlation between LOH and survival.     

Evidence for progression in frontal cortical pathology in late-stage Huntington's disease

Atrophy of the cerebral cortex in Huntington's disease is regionally heterogeneous and progressive, involving the entire cerebral mantle in terminal stages. Here, two areas (9 and 46) of the dorsolateral prefrontal cortex were analyzed in 11 late-stage (grades 3 or 4) Huntington's diseased patients and 8 normal control subjects. We used a 3-dimensional cell counting method to assess laminar cell density, number, and width. Reductions in overall cortical thickness in areas 9 (26%) and 46 (23%) were comparable. Area 9 exhibited loss of projection neurons in layers III (16%), V (31%), and VI (37%); these same layers were also reduced in width (25%, 34%, and 46%, respectively). In area 46, reductions in cortical width in layers II (18%) and VI (35%) were not accompanied by neuronal loss. Glial density was increased in deeper layers, reaching significance in layer VI (68%) of area 9 and in layer V (75%) of area 46; glial number was not altered. Thus, area 46 exhibited marked cortical thinning without apparent neuronal degeneration, whereas in area 9 neuronal loss was pronounced, consistent with an advanced phase of cortical pathology. Prominent involvement of corticothalamic neurons is discussed in the context of striatal loop circuitry and a possible pathologic cascade of cortical degeneration.     

An attempt to use Gore-Tex surgical membrane in lumbar disc surgery

BACKGROUND: Peridural fibrosis developing after lumbar discectomy may be responsible for as much as 20% of all Failed Back Surgery Syndrome. A variety of biological and non-biological materials have been used as a barrier to invasion of fibrous tissue into the vertebral canal. AIM: The purpose of this study was to evaluate the use of expanded polytetrafluoroethylene (ePTFE) surgical membrane (Gore-Tex membrane) to inhibit peridural fibrosis and reduce FBSS symptoms after lumbar discectomy. MATERIAL AND METHODS: In a prospective study we compared postoperative results in 20 patients who had an ePTFE membrane implanted during lumbar discectomy with the results in 20 patients in whom no material was implanted. The outcomes were evaluated using a questionnaire on activities of daily living according to the Low Back Outcome Score, pain grading scale -- Visual Analog Scale, assessment of Lasegue sign and MRI 18-24 months after the operation for all patients. RESULTS: The authors found no evident positive clinical and radiological effects of using ePTFE surgical membrane during lumbar discectomy. CONCLUSIONS: 1. It is impossible to prove that ePTFE membrane used during lumbar discectomy essentially prevents postoperative peridural scar formation. 2. The use of ePTFE membrane does not improve the outcome of the surgical treatment of lumbar disc herniation.     

Analysis of phacoemulsification complications during mastering of the method

PURPOSE: Intra-operative and postoperative complications of the first 50 phacoemulsifications were evaluated. The procedures were performed by one, skilled at ECCE surgeon. The phaco-chop technique was carried out in all cases with use of anterior chamber maintainer (ACM). MATERIAL AND METHODS: Eyes for surgery met the requirements: normal comea, presence of red reflex from the fundus and correct lens position. The patients were divided into 2 groups: I group--25 eyes had first surgery, II group--25 eyes had second surgery. On the first day after surgery complications and uncorrected acuity were evaluated. RESULTS: 50 eyes of 48 patients underwent operation. The mean age was 69.4 years 5% eyes had previous surgical record: 4--underwent trabeculectomy, 1--pars plana vitrectomy. The 12 intra-operative complications appeared in 10 eyes (20%): posterior capsule rupture without vitreous loss in 4% and 10% with vitreous loss, Descemet membrane detachment in 4%, iris dialysis in 2%, and persistent iris damage without sphincter disruption in 4%. The 16 postoperative complications concerned 10 eyes (20%): corneal oedema in 20%, transient intra-ocular pressure raise in 8%, hyphaema in 2%, and fibrin exudation in 2%. The majority of complications concerned the I group of eyes. The uncorrected visual acuity was 0.5 or better in 80% of eyes, on the first day after the operation. CONCLUSIONS: The use of ACM made the first steps in phacoemulsification rate during the learning course.     

Sequence variation in pertussis S1 subunit toxin and pertussis genes in Bordetella pertussis strains used for the whole-cell pertussis vaccine produced in Poland since 1960: efficiency of the DTwP vaccine-induced immunity against currently circulating B. pertussis isolates

The present study indicates that the appearance of the B. pertussis harbouring prn2 gene allele variant (not found among clinical isolates before 1990s) may have been induced by long-term vaccination in Poland with DTP-composed vaccine strains presenting exclusively prn1. However, ptxS1A allele of pertussis toxin subunit S1 encoding gene, predominant in the currently isolated B. pertussis strains, has been found in vaccine strains used for whole-cell pertussis component (wP) production of DTP vaccine in 1960-1978. This outrules the possibility that the appearance of ptxSIA allele might be related to vaccine pressure driven by non-ptxS1A vaccine strains used for long-term immunization with wP. Intranasal challenge animal model testing the efficiency of the clearance of B. pertussis strains harbouring different ptxS1/prn allele gene combinations revealed that currently produced DTwP vaccine may not contain adequate B. pertussis vaccine strains, since isolates with gene variants different from those observed in vaccine strains were eliminated from the lungs of the immunized animals with lower efficiency.     

Drinking patterns and problems in emergency services in Poland

AIMS: To examine drinking patterns and problems in emergency services in Poland, where both alcohol consumption and the health care system have undergone enormous recent change. METHODS: A probability sample of 734 emergency service patients was breathalyzed and interviewed in a large public hospital in Warsaw, Poland. RESULTS: 2.5% of the sample was breathalyzer positive; all were male and injured. Injured males were significantly more likely to report heavy problem drinking than non-injured, but no differences were found for females. Among injured males who reported drinking prior to the event, close to 50% reported feeling drunk, and over 75% attributed a causal association of their drinking with injury. CONCLUSIONS: These data point to substantial alcohol-involvement on the part of injured males in this population, and suggest emergency services may be a productive venue for identifying those patients who would benefit from a brief intervention.     

Changes in lymphocyte subsets in children with newly diagnosed type 1 diabetes mellitus

The aim of this study was to assess changes in selected peripheral blood lymphocyte subsets in children and adolescents with newly diagnosed type 1 diabetes mellitus (DM) and determine the correlation between these changes and other immunological markers. The study involved a group of 39 patients aged 2-14 years and a control group. The number of T- and B-lymphocytes and the number of CD4, CD8, CD4/HLA-DR, CD8/HLA-DR, CD5/CD20 subsets were measured by flow-cytometry using monoclonal antibodies. Islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GADA) were assessed. In both the diabetic and control groups the number of T-and B-lymphocytes were within normal limits. In patients with DM, the percentage of CD5+/CD20+ cells was significantly increased compared with the control group (p < 0.0001). ICA were positive in 80% of patients and GADA in nearly 65%. A positive correlation between the CD5/CD20 subset and ICA and GADA was found. In patients with a high percentage of CD5+/CD20+ lymphocytes, a higher percentage of activated subsets (CD4/HLA DR and CD8/ HLA DR) was detected. In conclusion: CD5/ CD20 lymphocyte subsets are a good additional marker of autoimmunological processes in DM.     

Effects of antenatal corticosteroids on regional brain and non-neural tissue water content in the ovine fetus

OBJECTIVE: We examined the effects of maternal corticosteroid administration on water content in regional tissue in ovine fetuses at 60%, 80%, and 90% of gestation. METHODS: After catheters were placed in the fetuses, the ewes were given four 6-mg doses of dexamethasone or placebo injections 12 hours apart over 48 hours. Water content of fetal tissue was determined 18 hours after the last injection was given to the ewes. Tissue water was determined by wet-to-dry weight ratio in brain (cerebral cortex, caudate nucleus, cerebellum, midbrain, and medulla) and non-neural tissues (kidney, liver, muscle, and skin) at each gestational age. RESULTS: Water content (P <.05) in brain regions was lower in fetuses from dexamethasone-treated than placebo-treated ewes at 60% but not 80% or 90% of gestation and in non-neural tissues at each gestational age. CONCLUSIONS: Maternal treatment with a corticosteroid regimen similar to that used in the clinical setting was associated with small decreases in brain water content early but not later in gestation. This corticosteroid treatment regimen was also associated with decreased regional non-neural tissue water content at 60%, 80%, and 90% of gestation.