THC and CBD effects on alcohol use among alcohol and cannabis co-users.

OBJECTIVE: Conflicting evidence exists regarding the effects of cannabis on alcohol consumption, with some studies suggesting that cannabis is a substitute for alcohol, whereas others suggest that cannabis complements alcohol, thereby increasing drinking. Cannabidiol (CBD) has shown preclinical promise in decreasing alcohol consumption. This study explores the effects of cannabis containing different potencies of CBD and delta-9-tetrahydrocannabinol (THC) on alcohol consumption. METHOD: In this naturalistic observational study, 120 cannabis and alcohol-using adults (mean age = 33.2 years, 39.2% female, 83.3% white) were assigned to use one of three legal-market cannabis strains (predominantly THC, predominantly CBD, and CBD + THC) ad libitum for 5 days. Timeline Followback data on drinking and cannabis use were collected at a baseline session pertaining to the 30 days prior to the ad libitum period, and data regarding alcohol and cannabis use during the 5-day period were collected at follow-up (FU), immediately following the 5-day period. RESULTS: Regression models tested strain differences in drinking outcomes during the ad libitum period. Orthogonal contrast codes were created comparing the CBD group with the other two groups and comparing the THC group with the CBD + THC group. The CBD group drank fewer drinks per drinking day (p < .05), had fewer alcohol use days (p < .05), and fewer alcohol and cannabis co-use days (p < .05) compared with the other groups. No differences emerged between the THC and the CBD + THC group. CONCLUSIONS: Cannabinoid content should be considered in studies of alcohol and cannabis co-use. Findings are consistent with preclinical work, suggesting that CBD may be associated with decreased alcohol consumption. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Subconjunctival carboplatin therapy and cryotherapy in the treatment of transgenic murine retinoblastoma.

OBJECTIVES: To determine the efficacy and dose response of subconjunctival carboplatin with and without cryotherapy in the treatment of murine transgenic hereditary retinoblastoma. METHODS: Fifty-one 5-week-old transgenic BLH SV-40 (Charles Rivers Laboratories, Boston, Mass) T-antigen-positive mice with retinoblastoma were administered 6 subconjunctival injections of carboplatin in 1 eye at drug doses of 10, 15, 20, 25, 62.5, 125, and 250 microg. Six control eyes received 6 subconjunctival injections of balanced salt solution. Fourteen of the 51 subconjunctivally treated eyes received a single application of transconjunctival cryotherapy immediately prior to each carboplatin injection. Six control eyes received 6 single applications of transconjunctival cryotherapy using the above schedule but did not receive carboplatin. All experimental and control eyes were obtained at 16 weeks of age for histopathologic examination. RESULTS: A dose-dependent inhibition of intraocular tumor growth by subconjunctivally delivered carboplatin was observed in these transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the mouse eyes at doses of 180 microg. In animals treated with cryotherapy alone, no tumor control was noted (0 of 6). In animals treated with subconjunctival carboplatin coupled with cryotherapy, a tumor control dose of 417 microg was found. No evidence of histopathologic treatment toxicity was noted. CONCLUSIONS: Subconjunctival delivery of carboplatin in serial doses effectively inhibits intraocular tumor growth in a dose-dependent fashion in a transgenic murine retinoblastoma model. Cryotherapy does not increase tumor control in this murine retinoblastoma model.

The history of surgery for ischemic heart disease.

Myocardial revascularization had its beginnings in the early 1900s with extracardiac operations, such as sympathetic denervation and thyroid ablation. From there it evolved through neovascularization via pericardial poudrage and cardiopexy in the 1930s to 1950s, to mammary artery myocardial implantation in the 1940s and endarterectomy in the 1950s, to saphenous vein- and mammary artery-coronary artery bypass grafting in the 1960s. The history of the surgical treatment of myocardial ischemia is presented here in chronologic sequence to highlight the prescient thinking and the persistence of efforts, as well as the false starts and the rediscovery of old ideas, that have marked the development of this treatment.

The history of interventional cardiology: cardiac catheterization, angioplasty, and related interventions.

The histories of cardiac catheterization, angioplasty, and other catheter interventions are spectacular journeys marked by undeterred genius, serendipity, and the vindication of the scientific method. Cardiac catheterization began with Hales's 1711 equine biventricular catheterization, other early experimental catheterizations in the nineteenth century, and Forssmann's dramatic 1929 right-heart self-catheterization. Cournand, Richards, and others finished unlocking the right heart in the 1940s; Zimmerman, Cope, Ross, and others unlocked the left heart in the 1950s; and the coronary arteries were inadvertently unlocked by Sones in 1958, leading to the advent of percutaneous femoral coronary angiography by Judkins and by Amplatz in 1967. Dotter's accidental catheter recanalization of a peripheral artery in 1963 ushered in the era of intervention, crowned by Gruentzig's balloon angioplasty in the mid-1970s and leading to today's panoply of devices used percutaneously to revascularize the coronary arteries in a variety of clinical settings.

History of drugs for thrombotic disease. Discovery, development, and directions for the future.

The history of the antithrombotic agents--aspirin, heparin, warfarin, and the thrombolytics--is a rich and lively odyssey of serendipity, perseverance, vision, and conflict involving a number of striking personalities. The history of aspirin spans ages and continents from Hippocrates' analgesic for women in labor to the rediscovery of the white willow bark by English country scholar Reverend Edward Stone. Bayer chemist Felix Hoffmann reinvented aspirin for his ailing father; suburban physician L.L. Craven pioneered the prophylactic antithrombotic uses of aspirin; and Sir John Vane elucidated aspirin's mechanism of action as the inhibition of prostaglandin synthetase. Heparin was discovered by McLean, working as a medical student in 1915 in search of a pure procoagulant in dog liver. His original impure material differed somewhat from today's heparin, but purified heparin was rapidly accepted for a myriad of clinical uses; to this day, diverse new properties of this complex glycosaminoglycan continue to be elucidated. The oral anticoagulants emerged from veterinary research in the 1920s on a hemorrhagic disorder afflicting cattle that consumed spoiled sweet clover hay. Several chance encounters led Karl Link and his University of Wisconsin team to the identification of dicumarol as the offending agent in 1939 and its widespread therapeutic use by Wright and others in the 1940s. Link later developed warfarin as a rodenticide, but its use in humans soon followed in the 1950s. Vitamin K was discovered in the 1930s; its involvement in the mechanism of the anticoagulant agents was not delineated until the 1970s. The intrinsic ability of clotted blood to liquify and the fibrinolytic properties of normal urine were noted in the 1800s. Tillett and Sherry's group stumbled on the fibrinolytic properties of streptokinase in the 1930s and pioneered the therapeutic use of streptokinase in the 1940s and of urokinase in the 1960s. Several teams found tissue-type plasminogen activator in various body sites beginning in the 1940s, leading to its cloning and widespread use in the 1980s; anisoylated plasminogen-streptokinase activator complex is an example of rational drug design. The discoverers of these diverse agents have not only provided physicians with a potent armamentarium of antithrombotic drugs but also helped elucidate much basic science and vividly demonstrated the merits of perseverance, independent thought, and adherance to the scientific method.

[Effect of a filter system on measurement data and bacterial contamination in lung function studies]. / Einfluss eines Filtersystems auf Messwerte und bakterielle Kontamination bei Lungenfunktionsuntersuchungen.

80 measurements of the airway resistance of 20 patients did not yield any significant differences with or without using a bacterial filter (Pall PF 30) (p = 0.1213). Likewise, lung function tests conducted in 61 further patients did not reveal any relevant changes caused by introducing the filter, in respect of the lung function parameters VKin, FEV1, PEF, FEF25, FEF50, FEF75 and TLCO. In these studies the flow receptors were examined for contamination by bacteria. The introduction of the bacterial filter reduced the total count of identified germs from 108, 615 to 307, i.e. by 99.7 per cent, the greatest contamination being found in those parts that were close to the patient (57.6% with filter, 97.1% without filter). Germs of the resident flora of the mouth and pharynx were identified, and occasionally also potential infectious agents such as staphylococcus aureus and streptococcus pneumoniae. The use of a filter system results in a marked decrease in the exposition to germs in lung function tests, without exercising any adverse effect on the measurement data (cross-contamination risk: 0.00078%). This is also achieved--albeit to a lesser extent--by changing those parts of the flow receptor that are close to the patient (cross-contamination risk: 0.0841%). Hence, the use of a filter system appears particularly meaningful in patients with considerable immunodeficiency (advanced stages of HIV infection).

[Biocompatibility studies of periodontal dressings]. / Untersuchungen zur Biokompatibilität von Parodontalverbänden.

Periodontal packs have to be considered medications due to their direct contact to the gums and wound surfaces. For this reason a high cell biological compatibility has to be considered as one of their most important properties. For this reason, the cytotoxicity of all periodontal packs commonly used in Germany was examined, using the "Erlangen Ciliate Test". This method, which is commonly used to determine the cytotoxic and cytostatic properties of a wide variety of different materials and substances, is based on liquid cultures of the eucaryotic organism "Tetrahymena piriformis", using an excellent correlation with mammalian or human tissue cultures as well as the LD50. A significant toxicity of up to 50% could be shown in all but one periodontal pack. In addition, the antibacterial properties of the same materials were examined, using liquid cultures of Staphylococcus aureus and hemolyzing streptococci group A. However, using this method, no significant antibacterial effects could be shown.

[Studies on the cytotoxicity of temporary relining materials in clinical use]. / Untersuchungen zur Zytotoxizität klinisch verwendeter temporärer Unterfütterungsmaterialien.

Temporary relining materials and surgical packs placed in a very intimate, direct contact to the adjacent epithelia or even wound surfaces are frequently used in dental and even more so in maxillofacial treatment procedures. Most of these materials, however, are not designed for this purpose; the results are inflammations and irritations. This study focussed on the cytotoxicity of the most frequently used temporary relining materials using the Erlangen ciliate test. This test method has been frequently used in various situations to determine the cytotoxic and cytostatic properties of substances and materials. It is based on liquid pure cultures of the eukaryotic monocellular organism "Tetrahymena piriformis". The sensitivity of these ciliates to cytotoxic noxae is rather similar to that of human and animal tissue cultures. Considerable differences in cytotoxicity have been observed.

[Bismuth--an environmental pollutant of the future]. / Wismut--Ein Umweltschadstoff der Zukunft?

Campylobacter pylori had become an interesting object in the discussion of the etiology of gastritis and peptic ulcer. Marshall was the first to describe antrum gastritis and duodenal ulcers as infectious diseases. Consequently new forms of therapy like antibiotics and bismuth salts were studied. In time the most favoured method of treatment is the administration of inorganic bismuth salts. There is a lack of recognition about the behaviour of this heavy metal in environment. 0.5 to 1 gram pure Bismuth per day and person leaves the patients naturally by faeces. The number of patients with gastric disorder is very large. Becomes bismuth a environmental problem in future?

[The problem of carcinogenic N-nitroso compounds--30 years old]. / Das Problem kanzerogener N-Nitroso-Verbindungen--30 Jahre alt.

For 30 years a correlation between N-nitroso compounds and cancer in man has been suspected. Investigations of nitrate and nitrite in food and human gastric cancer were performed all over the world. Literature on nitrosamines and nitrosamides is abundant, but it is impossible to make a realistic assessment of the danger of N-nitroso compounds and their precursors for man. Restriction of unnecessary intake of nitrate through drinking water and food is in any case an important task of hygiene.

[Dynamics of endogenous bacterial nitrite formation in the stomach. 2. Follow-up observations with standardized secretion from the porcine stomach]. / Dynamik der endogenen bakteriellen Nitritbildung im Magen. 2. Mitteilung: Verlaufsbeobachtung mit standardisiertem Sekret des Schweinemagens.

The bacterial nitrite synthesis in gastric juice from porcine stomach mucin and the decrease of nitrite after adding acid, which has often been described in literature-results of an examination with a standardizable biomodel. A decrease of nitrite concentration was only seen after adding a small volume acid of high concentration. Simulating the acid secretion by a large volume of low concentrated acid mixed with pepsin-solution (artificial gastric secrete, DAB 8) a considerable increase of nitrite concentration can be observed. An explanation can be the structure of stomach mucous gel can be solubilized in water and thus the ions are liberized inside of the stomach mucin. In the discussion of the endogenous synthesis of cancerogenic N-Nitroso-compounds it must be considered if this phenomena also can be observed in human secretes.

[Dynamics of endogenous bacterial nitrite formation in the stomach. 3. Dependence of nitrate and nitrite concentration on secretion volume]. / Dynamik der endogenen bakteriellen Nitritbildung im Magen. 3. Mitteilung: Abhängigkeit der Nitrat- und Nitritkonzentration vom Sekretvolumen.

The nitrate and nitrite concentration of 96 fasting gastric juice samples of young healthy volunteers were analysed. Two different methods have been used to take the gastric juice: 54 secrete samples were taken directly from the stomach, 42 secrete samples were taken after instillation of 500 ml sterile nitrite and nitrate free NaCl solution ("gastric-washing"). It could be shown that the expected high dilution of nitrite and nitrate concentration after gastric washing does not occur. A possible explanation might be that the solubilisation we could formerly observe in a biological pattern leads to a release of ions. This fact is very important for the question of endogen synthesis of cancerogenic N-nitroso compounds, because high nitrite and nitrate concentrations are subjects of interests as precursors of these compounds.

[Dynamics of endogenous bacterial nitrite formation in the stomach. 4. Localization and reciprocal action of nitrate and nitrite in the healthy human stomach]. / Dynamik der endogenen bakteriellen Nitritbildung im Magen. 4. Mitteilung: Lokalisation und Wechselwirkung von Nitrat und Nitrit im gesunden menschlichen Magen.

The nitrate and nitrite concentrations of 42 fasting gastric juice samples of young healthy human volunteers were analysed. It could be shown by separate determination of the concentration in the real secrete and the mucous gel that the amount of nitrate in the gel is about ten times higher than in the real secrete. The former conception, after which nitrate only gets by swallowed saliva into the stomach, has to be completed. It is obvious that the mucigenous glands of the stomach, like the saliva glands, are also able of nitrate enrichment and secretion. These results are very important for the evaluation of nitrate as a precursor of cancerogenic N-nitroso compounds.

[Dynamics of endogenous bacterial nitrite formation in the stomach. 5. Dependence of the nitrate concentration on the pH value of the stomach secretion]. / Dynamik der endogenen bakteriellen Nitritbildung im Magen. 5. Mitteilung: Abhängigkeit der Nitratkonzentration vom pH-Wert des Magensekrets.

The content of nitrate and nitrite was examined in the fasting gastric juice samples of 54 anamnestically healthy, young voluntary test-persons after at least 12 h of food abstinence. The analysis was made separately each time for the proper watery gastric juice as well as for the gastric mucus. It could be shown that significant differences exist between the concentration of nitrate and nitrite in the juice and the gastric mucus, that there is a pH-dependence in the concentration of nitrate in the juice and that the already earlier described gastric source of nitrate by the enrichment of nitrate ions in the juice producing glands of the gastric lining can be confirmed here too.

[Dynamics of endogenous bacterial nitrite formation in the stomach. 6. Redox potential and nitrite formation in stomach secretions]. / Dynamik der endogenen bakteriellen Nitritbildung im Magen. 6. Mitteilung: Redoxpotential und Nitritbildung im Magensekret.

The redox potential depending on the pH-value and the concentration of nitrite was examined in the fasting gastric juice samples of 132 anamnestically healthy, young, voluntary test-persons. It turned out that small pH-values (acid) are associated with high redox potentials and big pH-values (neutral) with smaller redox potentials. Therefore the hydrogen ion pressure (rH-value) resulting from these two quantities generally is situated in the indifferent range. Reducing properties of the whole juice can only occasionally be found, and apparently only then, if a neutral juice is acidified. Oxidizing properties have to be classified as exceptional cases. It cannot absolutely be traced on behalf of the findings, that can be raised with natural juices, if and when answered affirmatively, which effects the redox potential has on the formation of bacterial nitrite.

Evidence that epichlorohydrin is not a toxic metabolite of 1,2-dibromo-3-chloropropane.

The major urinary metabolite of 14C-epichlorohydrin, after oral administration to rats, was identified previously (Gingell et al. 1985) to be N-acetyl-S-(3-chloro-2-hydroxypropyl)-L-cysteine (ACPC) at 36% of the administered dose. In a similar study reported here, 1,2-dibromo-3-chloropropane (DBCP) was metabolized to at least 20 radioactive urinary metabolites. ACPC was only a minor metabolite (4%) of DBCP. Epichlorohydrin was metabolized in vitro by rat liver microsomes to alpha-chlorohydrin, but DBCP was not metabolized to epichlorohydrin or alpha-chlorohydrin under similar conditions. Covalent binding of radioactivity to liver microsomal proteins occurred for both substrates, but was less for 14C-epichlorohydrin than for 14C-DBCP. Addition of 3,3,3-trichloropropylene oxide, an inhibitor of epoxide hydrolase, increased the extent of protein binding of epichlorohydrin, but decreased the amount of 14C-DBCP which was bound. The data indicate the epichlorohydrin is not a significant in vivo nor in vitro metabolite of DBCP in the rat, and is unlikely to be responsible for the toxicity of DBCP.