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A new polycrystalline form of hydroxylapatite, CHA, has been shown to closely mimic dental enamel, in vitro, in regard to rate and degree of plaque formation and effectiveness of antiplaque drugs. The material has successfully been exploited as a standardized hydroxylapatite plaque growth substrate in conjuntion with a mass antidental plaque drug screening program.
Respirophonography is an objective method of measuring respiratory and adventicious sounds. Current techniques make a perfect, albeit somewhat tedious registering of these respiratory murmurs possible, which can then be analysed for frequency. In this paper the method is investigated for its applicability to drug screening and proved satisfactory in a double blind trial and a pilot study. During treatment with secretolytic drugs the pathological respiratory sounds change or cease. In the respirophonogram this is recognisable by the fact that the volume peaks are either displaced to another frequency area or that they disappear altogether. The frequency range 100--500 Hz is the most significant as far as the respiratory murmurs are concerned. The concepts familiar to the clinician experienced in auscultation are set out in an unaccustomed way in the frequency-volume diagram. The respirophonogram offers the advantage that it can be documented and that findings can therefore be compared objectively. From the point of view of the clinician respirophonography is despite its far reaching perfection already attained, still technically in a preliminary stage.
Urine samples (n = 300) were examined for drugs by thin-layer chromatography ("Drug Skreen", Brinkmann Corp.) and by the "Enzyme Multiplied Immunoassay Technique" ("Emit", Syav Corp.). The results of both methods were compared for the detection of opiates, barbiturates and amphetamines. In more than 90% of the determinations identical results were obtained with both methods. About 10% of the results of the Emit barbiturate assay differed from those of thin-layer chromatography and therefore had to be further investigated by gas liquid chromatography. It could be demonstrated that the barbiturate determination by the Emit system correlated better with the results of gas liquid chromatography. From the results of this study it is suggested that thin-layer chromatography is used as a screening test, and to confirm positive results with other methods such as Emit. If the abuse of barbiturates or opiates is suspected the corresponding Emit test should also be performed, even in cases of a negative thin-layer chromatography screening. Confirmation with a third method such as gas liquid chromatography is necessary, if thin-layer chromatography and Emit lead to divergent results.
The Freund's adjuvant technic, using killed Mycobacterium butyricum suspended in mineral oil, is a refined tool for anti-inflammatory drug evaluation. Its use has long been reserved for testing and not for screening due to technical problems in the preparation of valid animal models. After reviewing the methodology, the authors demonstrated that the availability of arthritic rats from a modern breeding center (Charles River France, SA, Elbeuf, France) make the procedure applicable to drug screening. This has both practical and economic advantages. The animals can be used as test organisms for drug evaluation 14 da after treatment. Three criteria for measuring the effectiveness of anti-arthritic drugs have been established: an arithritic index determined by examination of the 4 paws; changes in the erythrocyte sedimentation rate; and changes in levels of plasma fibrinogen. The curative activity of test substances can be evaluated by a single series of measurements of these 3 criteria after 14 da of treatment. This test was compared with 2 others; edema of the paw induced by the subcutaneous injection of kaolin or carrageenan, and was found to be superior.
A biological test system has been developed to assess the prophylactic activity of compounds against sporozoite-induced Plasmodium berghei malaria in mice. The procedure was designed to serve as the foundation of an effort to develop tissue schizonticidal drugs in a manner parallel to that of a previous system employed in the U.S. Arym Antimalarial Drug Development Program to screen compounds for blood schizonticidal activity. In tests with 35 known antimalarial compounds, the new screen was found to be in agreement 93% and 80%, respectively, when assessed compound activity was compared with results obtained in a definitive mouse causal prophylactic test and a rhesus monkey radical curative system.
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Coxsackievirus B4 (CVB4) is an enterovirus with one of the highest mortality rates following infection, yet research on it remains limited. To enhance the efficiency of CVB4 research, we developed the rCVB4-EGFP and rCVB4-NanoLuc reporter viruses. The replication kinetics of these reporter viruses in SH-SY5Y and HeLa cells were essentially consistent with those of the wild-type CVB4. A strong correlation was observed between the fluorescence and bioluminescence signals of rCVB4-EGFP and rCVB4-NanoLuc and viral titers at specific times postinfection. When evaluating the anti-CVB4 drug fluoxetine using these reporter viruses, the half-maximal effective concentrations derived from fluorescence signals, bioluminescence signal intensities, and viral genome copies were consistent. In In Vivo drug evaluations, because CVB4 can infect various tissues and organs, the bioluminescence signal of rCVB4-NanoLuc effectively demonstrated the antiviral effects of drugs, offering significant advantages over traditional tissue viral titer analysis. The reporter viruses exhibited reduced virulence compared with wild-type CVB4 both In Vitro, in SH-SY5Y and HeLa cells, and In Vivo, in ICR suckling mice. Although this reduced virulence may limit their application for studying pathogenic mechanisms, these reporter viruses can serve as highly efficient tools for high-throughput screening and evaluation of anti-CVB4 drugs, vaccines, and neutralizing antibodies.
The methods for barbiturate, opiate, methadone, and amphetamine have been modified for use with the American Monitor KDA. The modification, which incorporates automatic correction for endogenous lysozyme activity, was evaluated by comparing results obtained with the KDA for human urine samples containing known amounts of drug(s) with results obtained with the procedure recommended by Syva for the Gilford 3500. There was 98% agreement bewteen the two systems. Six calibrators and 40 samples can be assayed for all four drugs in about 2.5 h. The procedure has proven to be reliable for screening urine samples obtained from clients at a methadone treatment center.
The intradermal injection of certain drugs with antimitotic properties in the guinea pig resulted in localized areas of reversible hair loss or hair growth inhibition. The size of the affected field was related to the dose. This may provide a useful and simple method for the rapid screening of potentially useful agents for local cytostatic activity.
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Cardiac fibrosis, characterized by aberrant fibroblast activation and excessive extracellular matrix deposition, lacks target-specific therapies, largely due to the absence of longitudinal, scalable, and non-destructive in vitro screening platforms. Traditional end-point assays and resource-intensive stem cell models inherently preclude real-time monitoring of fibrotic progression. To overcome these limitations, this protocol describes the generation, optimization, and validation of a mouse collagen type I alpha 1 (Col1a1) promoter-driven adenoviral mCherry fluorescent reporter system (Ad-mCol1a1p-mCherry) in NIH/3T3 fibroblasts. The critical steps for recombinant adenovirus packaging, transduction optimization (multiplicity of infection) to minimize cytotoxicity, and the establishment of a robust transforming growth factor beta (TGF-β)-induced fibrosis model are detailed. By circumventing the need for cell fixation, this system enables direct and longitudinal monitoring of collagen transcription in live cells. The model's specificity and reliability are pharmacologically validated using the TGF‑β type I receptor (ALK5) inhibitor SB431542, with fluorescent readouts correlating with endogenous fibrotic markers quantified via reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Ultimately, this cost-effective platform provides an accessible tool for the high-throughput screening of novel antifibrotic agents, thereby accelerating translational cardiovascular research.
Effects of vasodilating drugs on microcirculation of the rat cremaster muscle were investigated microscopically. Topical application and intravenous injection of papaverine produced dilatation of arterioles. Cyclandelate applied topically dilated the arterioles to a considerable extent. Topical application of bamethan induced arteriolar dilatation while bamethan given intravenously constricted the arterioles. Kallikrein applied topically induced a slight dilatation of arterioles, and intravenous administration of kallikrein produced an appreciable vasodilatation. Topical administration of bradykinin produced a vasodilatation of arterioles of the rat cremaster muscle. These results indicate that direct action of a drug on the microcirculation can be properly evaluated by the microscopic method in the rat cremater muscle, if the drug is applied topically, in the vicinity of small vessels under study.
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Morphine and methamphetamine, which are excreted in the sweat, are detected by the use of routine serological and physicochemical techniques for urinary examinations. Screening for drug abuse can be done with the same accuracy of that of urine. Rapid excretion of the drug via kidney (within one day) is followed by a slow but steady excretion of the sweat gland. Methamphetamine given orally in a dose of 10 mg is excreted in the sweat at a constant rate (1.4 microgram/ml). No significant difference of the amount excreted by both systems is found. Alveolar lining seems to prevent the elimination of the volatile methamphetamine via respiration. Not only narcotics and stimulants, but also many alkaloids and barbituarates are excreted in the sweat and detected quantitatively by the same principles. The toxicological analysis of the sweat promises a new scope of forensic investigation.
The effects of hallucinogenic and nonhallucinogenic drugs were studied on two behavioral tests: (1) discriminated Sidman avoidance, using modified Bovet-Gatti profiles, which have been proposed as specific in detecting hallucinogenic activity and (2) a drug discrimination experiment. By the first method, the "hallucinogenic profile" was obtained with both hallucinogenic and nonhallucinogenic drugs and, at least as used here, was not a suitable screening method. In the drug discrimination experiment, data from the present study along with other available evidence suggest the potential value of this method for drug screening procedures.
Coronaviruses (CoVs) pose a significant threat to human health, as demonstrated by the COVID-19 pandemic. The large size of the CoV genome (around 30 kb) represents a major obstacle to the development of reverse genetics systems, which are invaluable for basic research and antiviral drug screening. In this study, we established a rapid and convenient method for generating reverse genetic systems for various CoVs using a bacterial artificial chromosome (BAC) vector and Gibson DNA assembly. Using this system, we constructed infectious cDNA clones of coronaviruses from three genera: human coronavirus 229E (HCoV-229E) of the genus Alphacoronavirus, mouse hepatitis virus A59 (MHV-59) of Betacoronavirus, and porcine deltacoronavirus (PDCoV-Haiti) of Deltacoronavirus. Since beta coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Middle East respiratory syndrome coronavirus (MERS-CoV) represent major human pathogens, we modified the infectious clone of the beta coronavirus MHV-A59 by replacing its NS5a gene with a fluorescent reporter gene to create a system suitable for high-throughput drug screening. Thus, this study provides a practical and cost-effective approach to developing reverse genetics platforms for CoV research and antiviral drug screening.
In this trial suramin, diethylcarbamazine, trichlorphon, levamisole, mebendazole, melarsonyl potassiu, Hoechst 33258 and tinidazole were administered to cattle infected with O. gibsoni and O. gutturosa to determine the usefulness of this screen in predicting the effect of drugs in man against. O. volvulus except for melarsonyl potassium which was macrofilarticidal against O. gutturosa but not O. gibsoni when cattle were slaughtered 6 weeks after treatment. It was concluded that cattle infected with O. gibsoni are a satisfactory substitute for chimpanzees infected with O. volvulus, as a tertiary screen for drugs against O. volvulus, but that their use would be restricted to centres in O. gibsoni endemic areas where the necessary facilities and specialised knowledge required to use cattle as experimental animals exist.
Phenotypic screens carried out with functional genomics or small molecules have led to novel biological insights, revealed previously unknown targets for drug discovery programs, and provided starting points for the development of first-in-class therapies. Despite being valuable research tools, genetic and compound screening also have significant limitations. This perspective aims to shed a light on those limitations and provide mitigation strategies when available, with a goal of helping phenotypic screening practitioners gain an understanding of how and when to best utilize either approach.