Resistance interference with effectiveness

Bicomponent technology has been used to introduce functional and novelty effects other than stretch to nylon fibers. For instance, antistatic yams are made by spinning a conductive carbon-black polymer dispersion as a core with a sheath of nylon (188) and as a side-by-side configuration (189). At 0.1—1.0% implants, these conductive filaments give durable static resistance to nylon carpets without interfering with dye coloration. Conductive materials such as carbon black or metals as a sheath around a core of nylon interfere with color, especially light shades. 

The effect of metalloids on the corrosion resistance of alloys also varies with the stability of polyoxyanions contained in their films. Phosphorus and carbon contained in iron-chromium-melalloid alloys do not produce passive films of phosphate and carbonate in strong acids, and so do not interfere with the formation of the passive hydrated chromium oxyhydroxide... 

All feed streams are sterilised before being metered into the fermentation vessel. Contaminants resistant to the antibiotic rarely find their way into the fermenter. When they find a way to contaminate media, their effects are so catastrophic that prevention is of paramount importance. A resistant, (3-lactamase producing, fast-growing bacterial contaminant can destroy the penicillin.5 The contaminants not only consume nutrients intended for the fungus, but also cause loss of pH control and interference with the subsequent extraction process. 

Several groups of drugs that bind to tubulin at different sites interfere with its polymerization into microtubules. These drugs are of experimental and clinical importance (Bershadsky and Vasiliev, 1988). For example, colchicine, an alkaloid derived from the meadow saffron plant Colchicum autumnale or Colchicum speciosum), is the oldest and most widely studied of these drugs. It forms a molecular complex with tubulin in the cytosol pool and prevents its polymerization into microtubules. Other substances such as colcemid, podophyllotoxin, and noco-dazole bind to the tubulin molecule at the same site as colchicine and produce a similar effect, albeit with some kinetic differences. Mature ciliary microtubules are resistant to colchicine, whereas those of the mitotic spindle are very sensitive. Colchicine and colcemid block cell division in metaphase and are widely used in cytogenetic studies of cultured cells to enhance the yield of metaphase plate chromosomes. 

Care must be taken when choosing an oil for rubber processing to ensure that its content of polar fractions is low. These polar fractions contain some of the most chemically active compounds in the oil. Polar materials are thought to interfere with cure characteristics and play a part in polymer degradation. These effects will also be accompanied by a drastic reduction in weather resistance, although usually heat resistance is not affected. 

Most treatment-resistant depressed patients have received inadequate therapy. Issues to be considered in patients who have not responded to treatment include the following (1) Is the diagnosis correct (2) Does the patient have a psychotic depression (3) Has the patient received an adequate dose and duration of treatment (4) Do adverse effects preclude adequate dosing (5) Has the patient been compliant with the prescribed regimen (6) Was treatment outcome measured adequately (7) Is there a coexisting or preexisting medical or psychiatric disorder (8) Was a stepwise approach to treatment used (9) Are there other factors that interfere with treatment ... 

Although this hydrolysis is usually fairly rapid it is desirable to obtain conditions of a general nature that would be likely (a) to effect the complete hydrolysis of the more resistant phosphorofluoridates, (6) to ensure homogeneity of the reaction mixture so as to avoid possible mechanical losses of oily material, and (c) to ensure that the hydrolysis does not proceed so far as to cause an accumulation of phosphate ions, which might interfere with the subsequent determination. 

Irreversible inhibition in an organism usually results in a toxic effect. Examples of this type of inhibitor are the organophosphorus compounds that interfere with acetylcholinesterase (see Box 7.26). The organophosphorus derivative reacts with the enzyme in the normal way, but the phosphory-lated intermediate produced is resistant to normal hydrolysis and is not released from the enzyme. 

Mecfianism of Action A fluoroquinolone that inhibits two enzymes, topoisomerase II and IV, in susceptible microorganisms. Therapeutic Effect Interferes with bacterial DNA replication. Prevents or delays resistance emergence. Bactericidal. Pharmacokinetics Well absorbed from the GI tract after PO administration. Protein binding 20%. Widely distributed. Metabolized in liver. Primarily excreted in urine. Half-life 7-14 hr. 

A dose of 1 at 30 mg/kg increased the effects of intravenous doses of epinephrine at 5 g/kg and of dl-noreplnephrine at 10 ug/kg on both blood flow and blood pressure. Intravenous phenoxybenzamine at 15 mg/kg plus tolazollne at 2 mg/kg prevented almost completely the actions of I on blood pressure and blood flow Intravenous reserpine at 2 mg/kg increased markedly the effects of I at 30 mg/kg on blood pressure and peripheral resistance, but converted the usual immediate, small, temporary increase in blood flow into an immediate, small, temporary decrease. These various responses would be expected from either a mild sympathomimetic amine or an inhibitor of the breakdown of endogenous catecholamines Indeed, I at 10 M, was found to inhibit the monoamlneoxldase of the rat s liver. If the dose of I used in these experiments were distributed into the same fraction of the body water as that estimated for the human body,the concentration in the plasma would be about 9 times that stated above as the effective concentration for inhibiting the mono amine oxIdase. It is possible that inhibition of monoamlneoxldase by I plays a part in inducing the effects of the oxime on blood vessels and blood pressure. It is possible also that I interferes with reuptake of catecholamines by nerve endings this possibility seems not to have been explored. 

It is a potent alpha-adrenergic blocking agent and only haloalkylamine used clinically. It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease. It interferes with the reflex adjustment of blood pressure and produces postural hypotension. It increases the cardiac output and decreases the total peripheral resistance. It also antagonizes cardiac arrhythmias provoked by catecholamines. Apart from these effects, phenoxybenzamine has other actions also e.g. antagonism of acetylcholine, histamine, 5-hydroxytryptamine (serotonin). However, the vasodilatation produced by phenoxybenzamine is because of alpha blockage. Adverse reactions are miosis, dryness of mouth, inhibition of ejaculation, palpitation, nasal stuffiness and in higher doses, postural hypotension and reflex bradycardia. 

Flucytosine is converted into the anti metabolite 5-fluorouracil that inhibits thymidilate synthetase, thereby disrupting DNA synthesis. It also interferes with protein synthesis by incorporation of fluorouracil into RNA in place of uracil. Although active against most Candida species, its spectrum of antifungal activity, overall, is narrow. Since resistance can develop rapidly it is usually coadministered with another agent and its main value is that it facilitates a reduction in the dose (and, presumably, the toxic effect) of amphotericin when co-prescribed in this way. The main adverse effects are marrow aplasia and hepatotoxicity. 

Trilostane is 13-17 hydroxysteroid dehydrogenase inhibitor that interferes with the synthesis of adrenal and gonadal hormones and is comparable to aminoglutethimide. Trilostane s adverse effects are predominantly gastrointestinal adverse effects occur in about 50% of patients with both trilostane and aminoglutethimide. There is no cross-resistance or crossover of side effects between these compounds. Trilostane is not available in the USA. 

Fulvestrant is a pure estrogen receptor antagonist that has been somewhat more effective than those with partial agonist effects in some patients who have become resistant to tamoxifen. ICI 164,384 is a newer antagonist it inhibits dimerization of the occupied estrogen receptor and interferes with its binding to DNA. It has also been used experimentally in breast cancer patients who have become resistant to tamoxifen. 

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