Synthesis and antiviral activity evaluation of 3'-fluoro-3'-deoxyribonucleosides: broad-spectrum antiviral activity of 3'-fluoro-3'-deoxyadenosine

Five 3'-fluorinated ribonucleosides were prepared and evaluated for their inhibitory properties against different viruses. The synthesis of these compounds was achieved by treatment of 2',5'-di-O-tritylated nucleoside analogues possessing a xylo-configuration with diethylaminosulfur trifluoride, followed by deprotection. 3'-Fluoro-3'-deoxyadenosine was active against a broad range of viruses, encompassing both DNA viruses [pox (vaccinia)], single-stranded (+) RNA viruses [picorna (polio, Coxsackie B), toga (sindbis, Semliki Forest)] and double-stranded RNA viruses (reo). In its antiviral activity spectrum 3'-fluoro-3'-deoxyadenosine clearly differed from those adenosine analogues that are known as inhibitors of S-adenosylhomocysteine hydrolase. 3'-Fluoro-3'-deoxyadenosine also proved effective in vivo, in inhibiting tail lesion formation in mice inoculated intravenously with vaccinia virus.     

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.     

Quantitative assessment of ALZ-50 immunoreactivity in Alzheimer's disease.

A quantitative assay for ALZ-50 immunoreactivity was evaluated in samples of superior temporal gyrus taken at autopsy from 13 Alzheimer patients and 11 controls. The assayable immunoreactivity appears to be stable for at least 24 hours postmortem but was lost with formalin fixation. The mean value of the Alzheimer patients was tenfold higher than that of the controls (P less than .002). The values of four Alzheimer samples overlapped with the low levels seen in controls, but no controls had elevated levels. In this sample population, therefore, the assay had a sensitivity of 69% and specificity of 100%.     

Activity measurements of the high-energy pure beta-emitters 89Sr and 90Y by the TDCR efficiency calculation technique.

The absolute activities of the pure beta-emitters 89Sr and 90Y have been determined by a direct method, namely the triple-to-double coincidence ratio (TDCR) efficiency calculation technique. This undertaking has extended further the number of radionuclides that have been standardized by this non-extrapolation liquid scintillation (LS) method. Both measurements were carried out within the framework of international key comparisons under the auspices of the International Bureau of Weights and Measures (BIPM). The TDCR results agreed well with those of other participating national laboratories, most using alternative (tracer) methods.     

Influence of mattress characteristics on house dust mite allergen concentration

BACKGROUND: Exposure to a high level of house dust mite allergens (HDMAs) is considered as a risk factor for HDM sensitization and development of asthma in genetically disposed people. Mattresses are one of the most important sources of HDMA in people's living environment. OBJECTIVE: The aim of this study was to evaluate the association between mattress characteristics and HDMA concentrations on mattresses. METHODS: Dust samples of mattress surfaces were taken to evaluate the level of Der p 1 allergen. All participants filled in a questionnaire about the type of mattress, the type of covering (upper layer) of the mattress, dwelling characteristics and cleaning habits. Humidity and temperature of the bedroom were measured at the time of dust sampling. RESULTS: One hundred and sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress was associated with a higher level of Der p 1 compared with cotton upper layer (2.6 vs. 0.8 microg/g Der p 1). Moreover, higher relative humidity (RH) was associated with significant higher concentrations and density of Der p 1. CONCLUSIONS: Two factors were associated with lower levels of Der p 1 found on mattresses, namely: a cotton upper layer of the mattress compared with a layer of synthetic material and lower RH at the time of sampling. As far as we know, the association between type of upper layer and concentration of Der p 1 has not been described before and could lead to the formulation of practical advices in order to reduce HDMA concentrations on mattresses.     

Neuronal cell bodies in the hypothalamic paraventricular nucleus mediate stress-induced renin and corticosterone secretion

The present studies were undertaken to determine the involvement of neurons in the hypothalamic paraventricular nucleus (PVN) in stress-induced renin secretion. The stressor was a 10-min conditioned emotional response (CER) paradigm. Bilateral electrolytic lesions in the PVN prevented the stress-induced increase in plasma renin activity (PRA), and plasma renin concentration (PRC). Stress-induced corticosterone secretion was also blocked, supporting the histological verification and suggesting that the lesion included corticosterone-releasing factor neurons in the PVN. Stress-induced renin secretion appears to be restricted to the PVN, as electrolytic lesions in the nucleus reuniens, dorsal and caudal to the PVN, did not prevent the stress-induced increase in either PRA or PRC. The next step was to determine whether cell bodies in the PVN or fibers of passage through the PVN mediate the stress-induced increase of these hormones. For this purpose, bilateral stereotaxic injections of the cell-selective neurotoxin ibotenic acid (10 micrograms/microliter; 0.3 microliters per side) were performed 14 days prior to the stress procedure. Histological evaluation of the tissue revealed cell death and lysis in the PVN. Ibotenic acid injection into the PVN prevented the effect of stress on PRA, PRC and corticosterone levels. None of the lesions prevented the stress-induced rise in plasma prolactin concentration. These results suggest that neurons in the PVN play an important role in mediating stress-induced increases in renin and corticosterone but not prolactin secretion.     

Five‐Year Follow‐up After Sacral Neuromodulation: Single Center Experience

Objective. We studied long‐term clinical efficacy of sacral neuromodulation (SNM) therapy in patients with refractory urgency incontinence (UI), urgency/frequency (UF) and voiding difficulty (VD), together with urodynamic data at baseline and six   months postimplant. Materials and Methods. Twenty‐two patients were implanted with a neurostimulator after a positive response to a percutaneous nerve evaluation test defined as a greater than 50% improvement in symptoms. Results. At five‐year follow‐up, the number of incontinent episodes and pad usage per day decreased significantly in 10 out of 15 UI patients. Two of five UF patients were successfully treated with SNM; the number of daily voids for all UF patients decreased from 25 to 19 and average voided volume increased from 98 to 212 mL. One of the two VD patients was able to void to completion. Mean first sensation of filling at the six‐month urodynamic investigation for the UI and UF patients increased from 78 to 241 mL and 141 to 232 mL, respectively, and the maximum bladder capacity increased from 292 to 352 mL and 223 to 318 mL, respectively. Five of 22 patients underwent device explant and one patient still has an inactive stimulator implanted. Conclusion. SNM is an effective treatment modality that offers sustained clinical benefit in the majority of patients with refractory UI, UF, and VD that do not respond to other, more conservative therapies.     

Changes in sexual behavior during a safety and feasibility trial of a microbicide/diaphragm combination: an integrated qualitative and quantitative analysis.

If proven effective, vaginal microbicides and diaphragms will likely be part of a larger HIV prevention model that includes condoms and other prevention strategies. It is, therefore, important to understand how introducing new prevention methods may affect overall patterns of sexual risk behavior. Data presented were collected as part of a safety and feasibility study of ACIDFORM gel with a diaphragm among 120 women in South Africa. Interviews were administered at enrollment and months 1, 3, 5, and 6 of the trial. Focus groups were conducted at trial exit. Frequency of sex increased significantly after enrollment. This increase appears to be owing to perceived protection from HIV and greater sexual pleasure afforded by the gel. Male condom use was high overall but increased significantly from enrollment. Data suggest this is because of increased partner involvement, increased negotiating power afforded by study participation, and provision of free condoms perceived to be of high quality.