The intrusiveness of sound: Laboratory findings and their implications for noise abatement

Environmental policy with regard to noise abatement has traditionally only considered whether the noise levels in a given setting are high enough to be deemed a source of annoyance, disturbance, or threat to well being. However, laboratory studies using both simple and more complex work-related tasks have shown that task-irrelevant sound, regardless of its intensity, intrudes upon cognitive processing and disrupts performance substantially; furthermore, its damaging effect does not diminish with repeated exposure to the sound over time. For tasks that require short-term memory processing (particularly the short-term maintenance of order information) sound assumes disruptive power if it is acoustically varying over its time course. However, other properties of sound (e.g., the semanticity of speech) can incur an additional cost if the primary task necessitates or tends to evoke the extraction of meaning. It will be argued that interference in each case is explained by reference to a conflict between two concurrent mental processes; that being demanded by the task and that being involuntarily applied to properties of the sound. Such harmful effects, as well as having direct consequences for the general well-being of those working in noisy environments, may have far reaching consequences for health insofar as extraneous sound is a feature of many safety-critical work settings. Implications for noise abatement policy are highlighted.     

Treatment of systemic lupus erythematosus.

The treatment of systemic lupus erythematosus (SLE) is mainly based on a number of "traditional" drugs such as corticosteroids, antimalarials, azathioprine and cyclophosphamide. However, this scenario is rapidly changing due to the introduction of new compounds. Some of these new agents have been successfully used in other diseases, while others are being specifically designed to interfere with the immune abnormalities seen in SLE. As our knowledge on the mechanisms of immune response increases, new drugs that can interfere with T and B cell interaction and activation, production of anti-dsDNA autoantibodies, immune-complexes deposition and cytokine activation have been developed and some of these are now under investigation in SLE. Although initial data regarding their safety and efficacy are encouraging, caution must be taken before these drugs are considered as the treatment of choice for specific SLE manifestations. Specifically, controlled clinical trials with sufficient number of patients are necessary. If the promising results already available are confirmed, the use of these drugs might represent the keystone in the future management of SLE and other autoimmune diseases.     

In vitro studies on the immunomodulatory effects of extracts of Osbeckia aspera

The methanolic extracts of 19 Jordanian plants were combined with seven different antibiotics and applied to check the inhibitory effects of the combination on the resistance of Pseudomonas aeruginosa. A resistant strain of Ps. aeruginosa, which was isolated from a patient and a standard strain of the same microorganism were used in this study. Our results showed that there are significant variations in the effects of some combinations used on the resistant and the standard strains probably due to structural changes. Almost all the plant materials used in combination with penicillin G and erythromycin allowed full growth of the standard strain, while the combination with some plant materials like Gundelia tournefortii L. and Lepidium sativum L. inhibited the growth of the resistant strain. Chloramphenicol, gentamicin and cephalosporin can be given advantageously with almost all the plant materials used with few exceptions on the resistant strain. Nalidixic acid activity was improved significantly when combined with all plant materials and tested on standard strain. On the other hand, its activity on the resistant strain was slightly improved using the same combinations.     

Molecular quantification of human beta-glucuronidase levels in a patient with Vohwinkel's syndrome

The skin must undergo the process of keratinization in order to perform its functions. During the process of differentiation, certain genes are activated while others are repressed, leading to changes in structural proteins and enzymes and in the synthesis of various lipids. An error in any of these steps can ultimately impair the process of keratinization. Vohwinkel's syndrome is the direct result of a defect in keratinization. Patients who have this epidermolytic palmoplantar keratoderma present clinically with hyperkeratosis of the stratum corneum. Hyperkeratosis has been linked to an increase in beta-glucuronidase levels. The authors studied the absolute concentration of human beta-glucuronidase in a patient with Vohwinkel's syndrome as determined through a double-antibody sandwich enzyme-linked immunosorbent assay and a Western blot assay of the blood, urine, and skin of the patient.     

Mechanism of action of angiotensin II in human isolated subcutaneous resistance arteries

1. Human isolated subcutaneous arteries were mounted in a myograph and isometric tension measured. In some experiments, intracellular calcium [Ca(2+)]i was also measured using fura-2. 2. Angiotensin II (100 pM - 1 microM) increased [Ca(2+)]i and tone in a concentration-dependent manner. The effects of angiotensin II (100 nM) were inhibited by an AT1-receptor antagonist, candesartan (100 pM). 3. Ryanodine (10 microM), had no effect on angiotensin II-induced responses, but removal of extracellular Ca(2+) abolished angiotensin II-induced rise in [Ca(2+)]i and tone. Inhibition of Ca(2+) entry by Ni(2+) (2 mM), also inhibited angiotensin II responses. The dihydropyridine, L-type calcium channel antagonist, amlodipine (10 microM), only partially attenuated angiotensin II responses. 4. Inhibition of protein kinase C (PKC) by chelerythrine (1 microM), or by overnight exposure to a phorbol ester (PDBu; 500 nM) had no effect on angiotensin II-induced contraction. 5. Genistein (10 microM), a tyrosine kinase inhibitor, inhibited angiotensin II-induced contraction, but did not inhibit the rise in [Ca(2+)]i, suggesting that at this concentration it affected the calcium sensitivity of the contractile apparatus. Genistein did not affect responses to norepinephrine (NE) or high potassium (KPSS). 6. A selective MEK inhibitor, PD98059 (30 microM), inhibited both the angiotensin II-induced contraction and rise in [Ca(2+)]i, but had no effect on responses to NE or KPSS. 7. AT1 activation causes Ca(2+) influx via L-type calcium channels and a dihydropyridine-insensitive route, but does not release Ca(2+) from intracellular sites. Activation of tyrosine kinase(s) and the ERK 1/2 pathway, but not classical or novel PKC, also play a role in angiotensin II-induced contraction in human subcutaneous resistance arteries.     

A concise review of the toxicity and carcinogenicity of dimethylarsinic acid

Dimethylarsinic acid (DMA) has been used as a herbicide (cacodylic acid) and is the major metabolite formed after exposure to tri- (arsenite) or pentavalent (arsenate) inorganic arsenic (iAs) via ingestion or inhalation in both humans and rodents. Once viewed simply as a detoxification product of iAs, evidence has accumulated in recent years indicating that DMA itself has unique toxic properties. DMA induces an organ-specific lesion — single strand breaks in DNA — in the lungs of both mice and rats and in human lung cells in vitro. Mechanistic studies have suggested that this damage is due mainly to the peroxyl radical of DMA and production of active oxygen species by pulmonary tissues. Multi-organ initiation-promotion studies have demonstrated that DMA acts as a promotor of urinary bladder, kidney, liver and thyroid gland cancers in rats and as a promotor of lung tumors in mice. Lifetime exposure to DMA in diet or drinking water also causes a dose-dependent increase in urinary bladder tumors in rats, indicating that DMA is a complete carcinogen. These data collectively suggest that DMA plays a role in the carcinogenesis of inorganic arsenic.     

In vivo evidence for K(Ca) channel opening properties of acetazolamide in the human vasculature

1. The selective carbonic anhydrase inhibitor acetazolamide is known to increase blood flow in several organs. Acetazolamide directly dilates isolated resistance arteries associated with activation of calcium-activated potassium (K(Ca)) channels. We examined both the presence and mechanism of the direct vascular action of acetazolamide in vivo in humans. 2. Forearm vasodilator responses of 30 healthy volunteers to infusion of placebo and increasing doses of acetazolamide (1-3-10 mg min(-1) dl(-1)) into the brachial artery were recorded by venous occlusion plethysmography, before and after local administration of L-NMMA (0.2 mg min(-1) dl(-1), an inhibitor of NO-synthase, n=6), indomethacin (5.0 microg min(-1) dl(-1), an inhibitor of prostaglandin synthesis, n=6), glibenclamide (10 microg min(-1) dl(-1), an inhibitor of K(ATP) channels, n=6), tetraethylammonium (0.1 mg min(-1) dl(-1), an inhibitor of K(Ca) channels, n=6) or placebo (NaCl 0.9%, n=6). Lower dosages of acetazolamide did not affect vascular tone (n=6). 3. Acetazolamide infusions increased forearm blood flow from 2.41+/-0.17 to 2.99+/-0.18, 4.09+/-0.26 and 6.77+/-0.49 ml min(-1) dl(-1) in the infused forearm (P:<0.001), with no significant changes in the non-infused forearm, blood pressure or heart rate. Acetazolamide-induced vasodilation was not inhibited by L-NMMA, indomethacin, or glibenclamide but was significantly attenuated by TEA (vasodilation: 23+/-6, 82+/-19, 241+/-38% versus 27+/-8, 44+/-22, 42+/-35%). 4. We conclude that acetazolamide exerts a direct vasodilator effect in vivo in humans mediated by vascular K(Ca) channel activation. This makes acetazolamide the first drug known that specifically modulates this channel.     

Pharmacokinetics of Plasmid DNA in the Rat

Purpose. The pharmacokinetics of plasmid DNA after IV bolus administration in the rat by following supercoiled (SC), open circular (OC), and linear (L) pDNA forms of the plasmid.Methods. SC, OC, and L pDNA were injected at 2500, 500, 333, and 250 g doses. The concentrations in the bloodstream of OC and L pDNA were monitored.Results. SC pDNA was detectable in the bloodstream only after a 2500 g dose, and had a clearance of 390(±50) ml/min and V_d of 81(±8) ml. The pharmacokinetics of OC pDNA exhibited non-linear characteristics with clearance ranging from 8.3(±0.8) to 1.3(±0.2) ml/min and a V_d of 39(±19) ml. L pDNA was cleared at 7.6(±2.3) ml/min and had a V_d of 37(±17) ml. AUC analysis revealed that 60(±10) % of the SC was converted to the OC form, and nearly complete conversion of the OC pDNA to L pDNA. Clearance of SC pDNA was decreased after liposome complexation to 87(±30) ml/min. However the clearance of OC and L pDNA was increased relative to naked pDNA at an equivalent dose to 37(±9) ml/min and 95(±37) ml/min respectively.Conclusions. SC pDNA is rapidly metabolized and cleared from the circulation. OC pDNA displays non-linear pharmacokinetics. Linear pDNA exhibits first order kinetics. Liposome complexation protects the SC topoform, but the complexes are more rapidly cleared than the naked pDNA.     

Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation

Human male volunteers were studied in a metabolic facility whilst they were fed randomized controlled diets. In eight volunteers there was a significant increase in faecal apparent total N:-nitroso compounds (ATNC) and nitrite excretion (P < 0.0001 and P = 0.046, respectively) when randomized doses of meat were increased from 0 to 60, 240 and 420 g/day over 10 day periods. Mean (+/- SE) faecal ATNC levels were 54 +/- 7 microg/day when the diets contained no meat, 52 +/- 11 microg/day when the diets contained 60 g meat/day, 159 +/- 33 microg/day with 240 g meat and 199 +/- 36 microg/day with 420 g meat. Higher concentrations of NOC were associated with longer times of transit in the gut (r = 0.55, P = 0.001) and low faecal weight (r = -0.51, P = 0.004). There was no significant decline in levels in individuals fed 420 g meat for 40 days. The exposures found on the higher meat diets were comparable with other sources of N:-nitroso compounds (NOC), such as tobacco smoke. Many NOC are known large bowel initiators and promotors in colon cancer, inducing G-->A transitions in codons 12 and 13 of K-ras. Endogenous NOC formation, combined with prolonged transit times in the gut, may explain the epidemiological associations between high meat/low fibre diets and colorectal cancer risk.