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PubMed2000

Effects of compounding drug-related stimuli: escalation of heroin self-administration.

Previous experiments have demonstrated that presenting independently established discriminative stimuli in compound can substantially increase operant responding maintained by food reinforcement or shock avoidance. Recently, this phenomenon was also shown to occur with cocaine self-administration. The present study further assessed the generality of these stimulus-compounding effects by systematically replicating them with heroin self-administration. Rats' nose-poke responses produced intravenous heroin (0.025 mg/kg per infusion) on a variable-ratio schedule when either a tone or a light was present. In the absence of these stimuli, responding was not reinforced. Once discriminative control by the tone and light had been established, the stimuli were presented in compound under extinction (with heroin discontinued) or maintenance conditions (with heroin available during test-stimulus presentations). In extinction, the tone-light compound increased responding approximately threefold compared to tone or light alone. Under maintenance conditions, compounding increased heroin intake approximately twofold. These effects closely matched those obtained earlier with cocaine. This consistency across pharmacological classes and across drug and nondrug reinforcers further confirms that (a) self-administered drugs support conditioning and learning in a manner similar to that supported by other reinforcers; and (b) multiple drug-related cues interact in lawful and predictable ways to affect drug seeking and consumption.

Animals↗
PubMedDate not supplied

Screening drug-like compounds by docking to homology models: a systematic study.

In the absence of an experimentally solved structure, a homology model of a protein target can be used instead for virtual screening of drug candidates by docking and scoring. This approach poses a number of questions regarding the choice of the template to use in constructing the model, the accuracy of the screening results, and the importance of allowing for protein flexibility. The present study addresses such questions with compound screening calculations for multiple homology models of five drug targets. A central result is that docking to homology models frequently yields enrichments of known ligands as good as that obtained by docking to a crystal structure of the actual target protein. Interestingly, however, standard measures of the similarity of the template used to build the homology model to the targeted protein show little correlation with the effectiveness of the screening calculations, and docking to the template itself often is as successful as docking to the corresponding homology model. Treating key side chains as mobile produces a modest improvement in the results. The reasons for these sometimes unexpected results, and their implications for future methodologic development, are discussed.

Computer Simulation↗
PubMedDate not supplied

[A review of the clinical application of dyes in gastrointestinal chromoendoscopy, and their magistral formulation].

OBJECTIVE: To review the drug compounding of dyes employed in chromoendoscopy, and their clinical effectiveness. METHOD: A literature search in Medline, Cochrane Library, and Micromedex was carried out with the term chromoendoscopy as a keyword, and the search was then repeated for each dye found in association with the term endoscopy. A number of monographs, scientific journals, and references quoted in selected papers were also reviewed. Papers collected were then classified according to their methodology. RESULTS: Ninety-six references were found, their original article being recovered for only 57 of these - 13 clinical trials, 21 case series, and 11 reviews. References were found for 7 dyes. Main indications, evidence of effectiveness, administration route, and drug formulation are described for each dye. CONCLUSIONS: The number of papers involved is high, but their accessibility is limited. Evidence is overall scarce, but high in cases such as methylene blue for Barrett s esophagus, lugol in the detection of esophageal carcinoma, and indigo carmine for colonic hyperplastic polyp differentiation. Drug compounding is rather simple, but scarcely developed.

Coloring Agents↗
PubMed1999

[Early use of Chinese drug rhodiola compound for patients with post-trauma and inflammation in prevention of ALI/ARDS].

OBJECTIVE: To evaluate the effects of the Chinese drug rhodiola on the preventive treatment of acute lung injury (ALI) caused by post-traumatic/inflammatory and thoracic-cardiovascular operations. METHODS: 104 patients who coincide with their diagnosis and standard scale were divided randomly in to single number groups A(1), B(1), C(1) and D(1) (early preventive treatment group EG) and double number groups A(2), B(2), C(2) and D(2) (control group CG). The treatment of primary disease both in EG and CG was similar, but in EG four grams of rhodiola compound (RCO) were used every day for a period of 3-15 days since admission and 5-7 days after operation. The indicators related to ALI in each groups were measured. RESULTS: PaO(2), AaDO(2) and hemorheology were significant in EG than in CG (P < 0.05) or (P < 0.01). The complication rate of ARDS was decreased about of 50.0% in EG than in CG. CONCLUSIONS: Early use of RCO may protect against major risk factors of ALI/ARDS caused by massive trauma/infection and thoracic-cardio-operations.

Adolescent↗
PubMed2006

A data base for partition of volatile organic compounds and drugs from blood/plasma/serum to brain, and an LFER analysis of the data.

Literature values of the in vivo distribution (BB) of drugs from blood, plasma, or serum to rat brain have been assembled for 207 compounds (233 data points). We find that data on in vivo distribution from blood, plasma, and serum to rat brain can all be combined. Application of our general linear free energy relationship (LFER) to the 207 compounds yields an equation in log BB, with R2=0.75 and a standard deviation, SD, of 0.33 log units. An equation for a training set predicts the test set of data with a standard deviation of 0.31 log units. We further find that the in vivo data cannot simply be combined with in vitro data on volatile organic and inorganic compounds, because there is a systematic difference between the two sets of data. Use of an indicator variable allows the two sets to be combined, leading to a LFER equation for 302 compounds (328 data points) with R2=0.75 and SD=0.30 log units. A training equation was then used to predict a test set with SD=0.25 log units.

Animals↗
PubMed1988

In vitro and in vivo studies evaluating a liposome system for drug solubilization.

A liposome system was developed which demonstrates suitability as an intravenous drug carrier for a lipophilic drug compound (RS-93522, a dihydropyridine CA2+ channel blocker). An aqueous phospholipid suspension was employed as a nontoxic solubilizing vehicle for this drug. The liposome formulation, composed of a 3% mixture of dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol, produced a physically and chemically stable preparation which solubilized the lipophilic drug compound at a concentration 500 times above its intrinsic aqueous solubility. Characterizing the liposome-drug system by gel filtration chromatography showed that the drug comigrated with the lipid constituents of the liposome. Further in vitro studies established that the liposome-RS-93522 formulation allowed for rapid and complete transfer of the drug from the liposome to bind with albumin when added to human serum. In vivo studies with rats were performed in which the pharmacokinetics of the liposomal-RS-93522 system were compared to those of a cosolvent-solubilized RS-93522 solution. This study showed that the pharmacokinetic profiles of the two solutions were identical. All the evidence indicates that a liposome formulation of this type does not alter the distribution of the drug in serum and is, therefore, not likely to affect the intrinsic pharmacological or toxicological parameters of the drug relative to the conventional solvent/excipient-containing formulation. This liposome system demonstrates utility as a biocompatible, nontoxic drug delivery vehicle.

Animals↗
PubMed2006

Air to fat and blood to fat distribution of volatile organic compounds and drugs: linear free energy analyses.

Partition coefficients, K(fat), from air to human fat and to rat fat have been collected for 129 volatile organic compounds, VOCs. A linear free energy relationship, LFER, correlates the 129 values of log K(fat) with R(2)=0.958 and a standard deviation, S.D., of 0.194 log units. Use of training and test sets gives a predictive assessment of around 0.20 log units. Combination of log K(fat) with our previously listed values of log K(blood) enables blood/plasma to fat partition coefficients, as log P(fat), to be obtained for 126 VOCs. These values can be correlated with R(2)=0.847, S.D.=0.304 log units; the latter is also our assessment of the predictive capability of the LFER. Values of log P(fat) have been collected for 46 drugs, and can be fitted to an LFER with R(2)=0.811 and S.D.=0.355 log units. Unlike partition into brain or muscle, the data for VOCs and drugs cannot be combined. There are marked discrepancies for PCBs for which partition from blood/plasma into fat is very much less than that calculated from the data on VOCs or from the data on drugs.

Adipose Tissue↗
PubMed2006

Contributions of Muhadhdhab Al-Deen Al-Baghdadi to the progress of medicine and urology. A study and translations from his book Al-Mukhtar.

This study of the Arabic 4-volume book of Al-Mukhtar Fi Al-Tibb (Choice Book on Medicine) written by the Muslim physician Muhadhdhab Al-Deen Al-Baghdadi (515-610 H, 1117-1213 AD) aimed at evaluating his contributions to the progress of medicine and urology along with providing English translations of relevant excerpts. Al-Baghdadi laid emphasis on the morals of medical practice and the principles of medical education describing how to select medical students and how to evaluate graduates. He stressed on the need for a long training program directly supervised by skilled expert doctors both in hospitals (Al-Bimaristanat) and during home visits. A good part of volume 1 was allocated to preventive medicine and the whole of volume 2 was devoted to the pharmacy section, which he restricted to what was proven by the experience of his teacher and by his own experiments. Same as all his predecessors in the Islamic era, Al-Baghdadi stressed the importance of clinical medicine and gave more details related to history taking, physical examination, differential diagnosis and prognosis. Similar to them, he also, emphasized that a doctor should be quite knowledgeable in anatomy. Furthermore, the presence of anatomical drawings in Kitab Al-Mukhtar Fi Al-Tibb is a further step forward in illustrating medical text books; a trend that flourished in the Islamic era reflecting the role of direct observations and experience. The detailed description of the functional anatomy of the uretero-vesical junction and the antireflux and micturition mechanisms given by Al-Baghdadi is contrary to that of Galen (130-200 AD) but conforms well to our contemporary understanding. In the conservative management of urinary stones, he described 70 simple and 13 compound drugs while those described by Pulus of Aegina (625-690 AD) were only 20 simple and 3 compound drugs. Furthermore, Al-Baghdadi's description of the instruments and techniques of urethral catheterization, perineal cystolithotomy and perineal cystolithotripsy using Al-Zahrawi's lithotrite is meticulous and reveals originality, dexterity and experience.

Anatomy↗
PubMed2004

Modification of radiation-induced acute oral mucositis in the rat.

PURPOSE: A new non-toxic drug (compound A) consisting of curcumin, alpha-tocopherol and sunflower oil was developed and its efficacy tested in the treatment of radiation-induced oral mucositis in the rat. MATERIAL AND METHODS: Mature (12 weeks old, 200-225 g) female Sprague-Dawley rats were used. While under general anaesthesia, the tongues of the animals were slightly extended outside and a region of the underside of the tongue was irradiated in-situ with single doses of 2.27 MeV beta-rays from a 5-mm diameter 90Sr/90Y plaque. The dose-rate of the source was about 10 Gy min(-1) at the surface of the mucus membrane. Irradiations and subsequent assessment of the lesion were carried out under general anaesthesia maintained by a 1.5% halothane/oxygen mixture. Six groups of animals were irradiated with single doses of 13.5, 15.0, 16.5 or 18Gy. One subgroup (radiation only) received no further treatment, while the other five groups received 0.5 ml day(-1) of either compound A, sunflower oil, alpha-tocopherol, curcumin or water containing 10% ethanol by oral gavage until the end of experiments. Mucosal ulceration (erosion of mucosal epithelium) was considered as an end-point. From the day after irradiation until any acute radiation-induced oral mucosal lesion had healed, the tongues of the animals were assessed daily for the presence of radiation-induced mucositis (mucosal ulceration). Quantal data for the incidence of radiation-induced mucositis were analysed using logit analysis and a dose-modification factor was obtained. RESULTS: There was a modest increase in ED50, the dose expected to cause mucositis in 50% of the animals after both alpha-tocopherol and sunflower oil were administered. This resulted in dose-modification factors of 1.05. While curcumin treatment resulted in a dose-modification factor of 1.09. Compound A significantly reduced the incidence of radiation-induced mucositis with a statistically significant dose-modification factor of 1.2 +/- 0.1. CONCLUSIONS: Curcumin and other components of compound A appeared to be effective in the prevention of radiation-induced oral mucositis. However, the overall effect observed with the combination drug (compound A) appeared greater than additive.

Animals↗
PubMed1998

Determination of illicit and/or abused drugs and compounds of forensic interest in biosamples by capillary electrophoretic/electrokinetic methods.

The application of capillary electrophoresis (CE) methods in forensic toxicology for the determination of illicit and/or misused drugs in biological samples is reviewed in the present paper. Sample pretreatments and direct injection modes used in CE for analysis of drugs in biological fluids are briefly described. Besides, applications of separation methods based on capillary zone electrophoresis or micellar electrokinetic chromatography with UV absorbance detection to (i) analysis of drugs of abuse, (ii) analysis of other drugs and toxicants of potential forensic interest and (iii) for metabolism studies are reviewed. Also, alternative CE methods are briefly discussed, including capillary isotachophoresis and separation on mixed polymer networks. High sensitivity detection methods used for forensic drug analysis in biological samples are then presented, particularly those based on laser induced fluorescence. A glimpse of the first examples of application of CE-mass spectrometry in forensic toxicology is finally given.

Body Fluids↗