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PubMedDate not supplied

Illicit traffic and abuse of cocaine.

There has been an increasing availability and abuse of cocaine in Canada in recent years. Cocaine abuse has spread from the affluent adult sectors of society to middle-income groups and the young, involving large sections of the population. The increase in illicit demand for, and the social acceptability of, cocaine has led to an increase in illicit cocaine supply. The availability of cocaine on the illicit market has been sustained by a vast over-production of the raw materials needed to produce cocaine in coca-growing areas of South America and the activities of sophisticated trafficking organizations with large operations and profits. As a result, cocaine prices at the wholesale level in South America and Canada are declining, and at the retail level in Canada have remained relatively stable or have slightly decreased. It has been estimated that more than one half of the amount of cocaine on the illicit market in Canada was illegally produced in Colombia, but the main quantities of the raw materials used for such production originated in Bolivia and Peru. Cocaine is smuggled into Canada primarily by commercial air transport, arriving at the three principal ports of entry, namely Montreal, Toronto and Vancouver, from whence it is distributed to other parts of the country. As drug law enforcement efforts increase in one area, traffickers shift their illicit operations to other areas in an attempt to escape detection. Current evidence suggests that both the availability and abuse of cocaine in Canada are likely to increase in the coming years.

Bolivia↗

PubMed1978

Epidemiology of poly-parasitism. IV. Combined effects on the state of health.

The assessment of morbidity caused by chronic parasitic infections in the populations of endemic areas has remained difficult and controversial. Contributing to this predicament is the frequent occurrence of multiple infections with agents that can cause a wide range of clinical manifestations, from the frequent symptomless carrier state to overt disease with more or less specific clinical manifestations. In the interpretation of the complex morbidity patterns found in rural populations of tropical countries, it is often difficult to make a clear determination of cause and effect. The situations is further complicated by the low degree of pathognomicity of the clinical manifestations of even the advanced stages of certain parasitic diseases. The paper gives examples that illustrate the interaction between endemic malaria and schistosomiasis as important causes of hepatosplenomegaly. Also shown in the paper are the inter-relationships between the nutritional status and the number of multiple infections with parasites found in African villages as well as the association between habitual coca leaf chewing, malnutrition and hookworm disease in a Peruvian community of mixed ethnic origin. The paper describes micro-epidemiological features of poly-parasitism by comparing the prevalence and intensity of infection with Onchocerca volvulus, Schistosoma mansoni and S; haematobium between sub-groups in the village population who have different sources of domestic water supply. In two African villages with endemic schistosomiasis where mass treatment will be administered, only 25% of the residents with parasitologically confirmed S. haematobium infection and 12% of those with S. mansoni had single infection; the remaining majority had at least one additional patent parasitic infection of public health importance.

Adolescent↗

PubMed1986

Myocardial infarction with topical cocaine anesthesia for nasal surgery.

Cocaine, the active alkaloid in coca leaf, is widely used as local anesthetic for otolaryngologic procedures. Our patient suffered an acute nontransmural myocardial infarction following clinical use of cocaine as topical anesthesia for nasal surgery, the first such case to be documented, to our knowledge. Although evidence documenting its cardiovascular toxicity is listed in contemporary pharmacologic literature, clinical cardiac injury has been reported to date only with the recreational use of cocaine. Authentic documentation of drug composition when received through the intervention of illicit vendors is always difficult. The literature is reviewed, justifying the use of cocaine as the most popular topical anesthetic in otolaryngologic practice. However, we hope that awareness of this possible complication will create a resurgence of research interest in topical cocaine anesthesia.

Adult↗

PubMed2006

Bile acid salt binding with colesevelam HCl is not affected by suspension in common beverages.

It has been previously reported that anions in common beverages may bind to bile acid sequestrants (BAS), reducing their capacity for binding bile acid salts. This study examined the ability of the novel BAS colesevelam hydrochloride (HCl), in vitro, to bind bile acid sodium salts following suspension in common beverages. Equilibrium binding was evaluated under conditions of constant time and varying concentrations of bile acid salts in simulated intestinal fluid (SIF). A stock solution of sodium salts of glycochenodeoxycholic acid (GCDC), taurodeoxycholic acid (TDC), and glycocholic acid (GC), was added to each prepared sample of colesevelam HCl. Bile acid salt binding was calculated by high-performance liquid chromatography (HPLC) analysis. Kinetics experiments were conducted using constant initial bile acid salt concentrations and varying binding times. The affinity, capacity, and kinetics of colesevelam HCl binding for GCDC, TDC, and GC were not significantly altered after suspension in water, carbonated water, Coca-Cola, Sprite, grape juice, orange juice, tomato juice, or Gatorade. The amount of bile acid sodium salt bound as a function of time was unchanged by pretreatment with any beverage tested. The in vitro binding characteristics of colesevelam HCl are unchanged by suspension in common beverages.

Allylamine↗

PubMed1997

1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor.

Nearly complete sequence-specific 1H, 13C, and 15N resonance assignments are reported for the backbone atoms of the receptor-binding domain of vascular endothelial growth factor (VEGF), a 23-kDa homodimeric protein that is a major regulator of both normal and pathological angiogenesis. The assignment strategy relied on the use of seven 3D triple-resonance experiments [HN(CO)CA, HNCA, HNCO, (HCA)CONH, HN(COCA)HA, HN(CA)HA, and CBCA-(CO)NH] and a 3D 15N-TOCSY-HSQC experiment recorded on a 0.5 mM (12 mg/mL) sample at 500 MHz, pH 7.0, 45 degrees C. Under these conditions, 15N relaxation data show that the protein has a rotational correlation time of 15.0 ns. Despite this unusually long correlation time, assignments were obtained for 94 of the 99 residues; 8 residues lack amide 1H and 15N assignments, presumably due to rapid exchange of the amide 1H with solvent under the experimental conditions used. The secondary structure of the protein was deduced from the chemical shift indices of the 1H alpha, 13C alpha, 13C beta, and 13CO nuclei, and from analysis of backbone NOEs observed in a 3D 15N-NOESY-HSQC spectrum. Two helices and a significant amount of beta-sheet structure were identified, in general agreement with the secondary structure found in a recently determined crystal structure of a similar VEGF construct [Muller YA et al., 1997, Proc Natl Acad Sci USA 94:7192-7197].

Binding Sites↗

PubMed1995

A fiber-optic cocaine biosensor.

A fiber-optic biosensor was developed for detection of cocaine, its metabolites, and other coca alkaloids, using a monoclonal antibody (mAb) against a derivatized benzoylecgonine (BE). The mAb was immobilized noncovalently on quartz fibers and a flow fluorometer was used to detect changes in evanescent wave fluorescence. A fluorescein (FL) conjugate of BE bound to the mAb specifically in a saturable manner and with high affinity (Kd = 7.6 nM). Cocaine or other test compounds competed with FL-BE for binding to the mAb in a concentration-dependent manner, thereby reducing the initial rate or steady-state fluorescence. Addition of cocaine to the flow buffer after reaching steady-state fluorescence enhanced the dissociation of bound FL-BE, and cocaine removal allowed fiber regeneration for multiple measurements. The detection limits for cocaine, cocaethylene, norcocaine, and BE were 5, 5, 29, and 30 ng/ml, respectively, but for ecgonine it was 4600 ng/ml and for methylecgonine it was 2000 ng/ml. Tropacocaine was detected at 10 ng/ml, but atropine was detected at 2900 ng/ml. The biosensor discriminated by 833-fold between cocaine and its stereoisomer pseudococaine. Structural features necessary for high-affinity recognition by this mAb are benzoate and 3 beta configuration, both of which are found in BE, cocaine, norcocaine, and cocaethylene.

Antibodies, Monoclonal↗

PubMed2001

Triple resonance solid state NMR experiments with reduced dimensionality evolution periods.

Two solid state NMR triple resonance experiments which utilize the simultaneous incrementation of two chemical shift evolution periods to obtain a spectrum with reduced dimensionality are described. The CO N CA experiment establishes the correlation of (13)C(i-1) to (13)C alpha(i) and (15)N(i) by simultaneously encoding the (13)CO(i-1) and (15)N(i) chemical shifts. The CA N COCA experiment establishes the correlation (13)Ca(i) and (15)CO(i) to (13)C alpha(i-1) and (15)N(i-1) within a single experiment by simultaneous encoding of the (13)C alpha(i) and (15)N(i) chemical shifts. This experiment establishes sequential amino acid correlations in close analogy to the solution state HNCA experiment. Reduced dimensionality 2D experiments are a practical alternative to recording multiple 3D data sets for the purpose of obtaining sequence-specific resonance assignments of peptides and proteins in the solid state.

Amino Acids↗

PubMed1994

1H, 13C and 15N NMR backbone assignments and secondary structure of the 269-residue protease subtilisin 309 from Bacillus lentus.

1H, 13C and 15N NMR assignments of the backbone atoms of subtilisin 309, secreted by Bacillus lentus, have been made using heteronuclear 3D NMR techniques. With 269 amino acids, this protein is one of the largest proteins to be sequentially assigned by NMR methods to date. Because of the size of the protein, some useful 3D correlation experiments were too insensitive to be used in the procedure. The HNCO, HN(CO)-CA, HNCA and HCACO experiments are robust enough to provide most of the expected correlations for a protein of this size. It was necessary to use several experiments to unambiguously determine a majority of the alpha-protons. Combined use of HCACO, HN(COCA)HA, HN(CA)HA, 15N TOCSY-HMQC and 15N NOESY-HMQC experiments provided the H alpha chemical shifts. Correlations for glycine protons were absent from most of the spectra. A combination of automated and interactive steps was used in the process, similar to that outlined by Ikura et al. [(1990) J. Am. Chem. Soc., 112, 9020-9022] in the seminal paper on heteronuclear backbone assignment. A major impediment to the linking process was the amount of overlap in the C alpha and H alpha frequencies. Ambiguities resulting from this redundancy were solved primarily by assignment of amino acid type, using C alpha chemical shifts and 'TOCSY ladders'. Ninety-four percent of the backbone resonances are reported for this subtilisin. The secondary structure was analyzed using 3D 15N NOESY-HMQC data and C alpha secondary chemical shifts. Comparison with the X-ray structure [Betzel et al. (1992) J. Mol. Biol., 223, 427-445] shows no major differences.

Amino Acid Sequence↗

PubMed1993

Contribution of aluminum from packaging materials and cooking utensils to the daily aluminum intake.

Migration of aluminum (Al) from packaging materials and cooking utensils into foods and beverages was determined at intervals during cooking or during storage by graphite furnace atomic absorption spectroscopy. High amounts of Al migrated into acidic products such as mashed tomatoes during normal processing in normal, non-coated Al pans. After 60 min cooking an Al content of 10-15 mg/kg was measured in tomato sauce. Surprisingly, the Al concentration was also increased up to 2.6 mg/L after boiling tap water for 15 min in Al pans. Storage of Coca-Cola in internally lacquered Al cans resulted in Al levels below 0.25 mg/L. In contrast, non-coated Al camping bottles containing lime blossom tea acidified with lemon juice released up to 7 mg Al/L within 5 days. The Al concentration in coffee was lower than that of the tap water used in its preparation, even if prepared in Al heaters. In Switzerland, where most pans nowadays are made of stainless steel or teflon-coated Al, the average contribution for the use of Al utensils to the daily Al intake of 2-5 mg from the diet is estimated to be less than 0.1 mg.

Aluminum↗

PubMed1992

A triple-resonance pulse scheme for selectively correlating amide 1HN and 15N nuclei with the 1H alpha proton of the preceding residue.

A 3D 1H-15N-13C triple resonance experiment is presented that contains exclusively cross peaks between the 1HN and 15N nuclei of one residue with the H alpha of the preceding residue. The pulse sequence, designed to minimize the time coherence, is transverse on nuclei with short T2 values. The experiment consists of coherence transfers via one-bond couplings from the HN via N, CO, C alpha to the H alpha and back to the HN for detection; it is called HN(COCA)HA. The experiment was tested on uniformly 15N- and 13C-enriched T4 lysozyme.

Amides↗

PubMed1980

[Reciprocal action between caffeine, other stimulants and drugs].

Caffeine is ingested not only with beverages as coffee, tea, coca-cola but also in form of many analgetic drugs. Therefore interactions of this substance with other biologically active substances and drugs should be expected, and the knowledge of these would be of practical importance. The interactions between caffeine and alcohol, smoking, salicylic acid, phenacetin, barbiturates, and theobromine are described.

Analgesics↗

PubMed1992

The role of nicotine in tobacco use.

The 1988 US Surgeon General's Report titled "Nicotine Addiction", is cited frequently in the literature as having established the "fact" that nicotine derived from cigarette smoke is addictive in the same sense as "classic" addicting drugs such as heroin and cocaine. This manuscripts critically evaluates key research findings used in support of this claim and identifies shortcomings in the data that seriously question the logic of labeling nicotine as "addictive". In addition, the manuscript argues that the role of nicotine in tobacco use is not like the role of cocaine in coca leaf use as argued by the 1988 Surgeon General's Report, but is, in fact, more like the role of caffeine in coffee drinking as concluded in the 1964 US Surgeon General's Report.

Humans↗

PubMed1989

Determining normal bolus size for thin liquids.

In order to define a suitable volume of barium to be delivered to patients during the radiographic evaluation of pharyngoesophageal function during swallowing, three different age groups of nondysphagic volunteers were studied. Subjects randomly swallowed boluses of water, barium, and Coca-Cola. The size of a normal thin liquid bolus was 21 ml (SD +/- 5 ml). We intend to include this information to compare different bolus sizes in cineradiographic examination of patients with swallowing complaints.

Cineradiography↗

PubMed2005

Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men.

In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.

Adult↗

PubMed2004

Relationship between dental erosion, soft drink consumption, and gastroesophageal reflux among Icelanders.

The aim of this study was to determine the prevalence of dental erosion in young Icelandic adults (19-22 years old) and patients with gastroesophageal reflux disease (GERD), in relation to their soft drink consumption and gastroesophageal reflux. Eighty subjects (40 males and 40 females), comprising 57 young adults (mean age 21 +/- 2 years) and 23 GERD patients (mean age 35 +/- 10 years), were enrolled in this study. All subjects answered a detailed frequency questionnaire of soft drink consumption and participated in a clinical examination. Erosion was scored for incisor and molar teeth separately. No significant difference was observed in the prevalence of dental erosion between young adults and GERD patients. However, by combining the two study groups a three-fold higher risk of having erosion in molars or incisors was found for subjects drinking Coca-Cola three times a week or more often ( p < 0.05). Additionally, significantly higher erosion scores were found in molars among subjects drinking more than 1 litre of carbonated drinks (all brands) per week ( p < 0.05). It is concluded that the frequency of soft drink consumption is a strong risk factor in the development of dental erosion.

Adult↗

PubMed2005

Pentaethylene-terephthalate (PET) bottles: a new device for autoerotic strangulation of the penis causing serious injury.

Strangulation of the penis by application of constricting devices may present a challenge for the treating physician. Depending on the type of constricting material, special equipment is essential for successful removal of the foreign bodies. We report a new form of constricting device, the neck of a Coca Cola bottle made of Pentaethylene-terephthalate (PET). Particular difficulties were encountered upon removal. Technical details of this case are described. Prior literature on the treatment of penile strangulation is discussed.

Aged↗

PubMed2004

Biologic poisons for pain.

Pain therapies from natural sources date back thousands of years to the use of plant and animal extracts for a variety of painful conditions and injuries. We certainly are all familiar with modern uses of plant-derived analgesic compounds such as opium derivatives from papaverum somniferum and salicylates from willow bark (Salix species). Local anesthetics were isolated from coca leaves in the late 1800s. Sarapin, derived from carnivorous pitcher plants, has been injected for regional analgesia in human and veterinary medicine, but efficacy is controversial. Biologic organisms can play important roles in developing an understanding of pain mechanisms, either from isolation of compounds that are analgesic or of compounds that produce pain, hyperalgesia, and allodynia.

Animals↗

PubMed1996

1-Methylpyrrolidine-2-acetic Acid is not a Precursor of Tropane Alkaloids.

1-Methylpyrrolidine-2-acetic acid and related compounds were studied as precursors in the biosynthesis of the tropane alkaloids in Erythroxylum coca and Datura innoxia. (R,S)-[1',2-(13)C2,2-(14)C,(15)N]-1-methylpyrrolidine-2- acid, (R,S)-[1',2'-(13)C2,1'-(14)C]-1-methylpyrrolidine-2-acetic acid, (R,S) [1',2'-(13)C2,1-(14)C]-1-methylpyrrolidine-2-acetate, and (R,S)-+2'-(14)C] methylpyrrolidine-2-acetic acid N-acetylcysteamine thioester were synthesized an intact plants by leaf-planting or hydroponic-feeding. Specific incorporation of compounds into ( - )-hyoscyamine, ( - )-scopolamine, ( - )-cocaine and the biosynthetically related cuscohygrine were very low. These results indicate that 1-methylpyrrolidine acid is not an efficient precursor of tropane alkaloids.

Alkaloids↗