Cannabinoids Drugs and Oral Health—From Recreational Side-Effects to Medicinal Purposes: A Systematic Review

Background: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in most of these, the prevalence of marijuana use has markedly risen over the last decade. At the same time, there is also a higher prevalence in the health concerns related to cannabis use and abuse. Thus, it is mandatory for oral healthcare operators to know and deal with the consequences and effects of cannabis use on oral cavity health. This review will briefly summarize the components of cannabis and the endocannabinoid system, as well as the cellular and molecular mechanisms of biological cannabis action in human cells and biologic activities on tissues. We will also look into oropharyngeal tissue expression of cannabinoid receptors, together with a putative association of cannabis to several oral diseases. Therefore, this review will elaborate the basic biology and physiology of cannabinoids in human oral tissues with the aim of providing a better comprehension of the effects of its use and abuse on oral health, in order to include cannabinoid usage into dental patient health records as well as good medicinal practice. Methods: the paper selection was performed by PubMed/Medline and EMBASE electronic databases, and reported according to the PRISMA guidelines. The scientific products were included for qualitative analysis. Results: the paper search screened a total of 276 papers. After the initial screening and the eligibility assessment, a total of 32 articles were considered for the qualitative analysis. Conclusions: today, cannabis consumption has been correlated to a higher risk of gingival and periodontal disease, oral infection and cancer of the oral cavity, while the physico-chemical activity has not been completely clarified. Further investigations are necessary to evaluate a therapeutic efficacy of this class of drugs for the promising treatment of several different diseases of the salivary glands and oral diseases.     

Permeation and skin retention of quercetin from microemulsions containing Transcutol® P

A microemulsion for the cutaneous release of quercetin was prepared. An aqueous phase, containing 40% Transcutol(?) P as solubilizing agent and permeation enhancer, was emulsified with Labrafil(?) as oil phase and Labrasol(?)/Capryol(?) 90 as Solvent/Co-solvent. Quercetin was dissolved in the microemulsion at the concentration of 1%. Ternary phase diagrams were generated to determine the optimal concentration of each excipient composing the microemulsion. The physicochemical properties of the microemulsion, such as pH, viscosity, refractive index, and particle size distribution were determined. The microemulsion was stable for 12 months at the storing conditions of 25.0 ± 1.0°C. The in vitro quercetin permeability into and through the abdominal hairless pig skin was determined by vertical Franz's cells. Quercetin showed hardly any permeability through the skin when dissolved in water- and Transcutol(?) P-free media, whereas a remarkable increase in cutaneous permeability was observed when quercetin was formulated in the microemulsion or when simply dissolved in Transcutol(?) P. These two last formulations are those showing the lower skin retention.     

Membranes of cellulose triacetate produced from sugarcane bagasse cellulose as alternative matrices for doxycycline incorporation

Cellulose triacetate (CTA) membranes were prepared using polyethylene glycol, 600 g mol^?1, (PEG) as additive and were utilized in essays of doxycycline (DOX) incorporation using two different procedures: (i) incorporation of the drug during the membrane preparation and (ii) incorporation of the drug to a previously prepared membrane. In the first, the produced membrane presented high compatibility between DOX and CTA, what was evidenced by analyzing the DSC curve for a CTA/PEG 50%/DOX system. Results showed that the drug is homogeneously distributed throughout the matrix, molecularly. In the second method, the drug was molecularly and superficially adsorbed, as seen through the DSC curve for the system CTA/PEG 10%/DOX, which nearly does not present alterations in relation to the original material, and through the isotherm of drug adsorption that follows the Langmuir model. Results showed that the membranes produced from sugarcane bagasse are adequate to produce matrices for drug‐controlled release, both for enteric use (Method (i)) and topic use (Method (ii)). © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Insights on Metabolic Reprogramming and Its Therapeutic Potential in Acute Leukemia

Acute leukemias, classified as acute myeloid leukemia and acute lymphoblastic leukemia, represent the most prevalent hematologic tumors in adolescent and young adults. In recent years, new challenges have emerged in order to improve the clinical effectiveness of therapies already in use and reduce their side effects. In particular, in this scenario, metabolic reprogramming plays a key role in tumorigenesis and prognosis, and it contributes to the treatment outcome of acute leukemia. This review summarizes the latest findings regarding the most relevant metabolic pathways contributing to the continuous growth, redox homeostasis, and drug resistance of leukemia cells. We describe the main metabolic deregulations in acute leukemia and evidence vulnerabilities that could be exploited for targeted therapy.     

Phase II study of 5-fluorouracil and adriamycin in transitional cell carcinoma of the urinary tract

A prospective study was carried out to determine the effectiveness and tolerance of the combination of 5-fluorouracil (600 mg/m2) and Adriamycin (50 mg/m2) given iv every 3 weeks to patients with disseminated transitional cell carcinoma of the urinary tract. Twenty-one of 23 patients entered in the study were evaluable for both response and toxicity. Two patients had complete responses and six had partial responses (greater than or equal to 50% reduction), yielding an overall response rate (complete plus partial) of 38%. Leukopenia (72.7%) and thrombocytopenia (54.5%) were common. Toxicity was life-threatening in one patient. Other common side effects were alopecia, nausea and vomiting, and a generalized feeling of weakness. Responders had a median survival time of 29 weeks compared to a median survival time of 9 weeks for nonresponders.     

Quantitative determination of mesophase content in pitch

A quantitative microscopy method for measuring the mesophase content in pitch has been developed because conventional solubility methods often do not reflect mesophase contents accurately. The general technique utilizes area measurements on photomicrographs of polished specimens to determine volume percent mesophase. Slight modifications to the general method are necessary to overcome unique problems associated with measurements on low (0–15%), intermediate (15–70%) and high (70–100%) mesophase content pitches. Typical data are presented for samples from each regime. The limitations of the method are discussed.     

Lipid composition of liver mitochondria and microsomes in hyperthyroid rats

Triiodothyronine-induced alteration of the lipid pattern in rat-liver mitochondria and microsomes has been investigated. In mitochondria, a 25% total cholesterol decrease and a 14% phospholipid increase have been detected. In these hyperthyroid rat liver organelles, a strong decrease in the total cholesterol/phospholipid molar ratio occurs. On the contrary, in microsomes from the same animals, a decrease of about 23% has been measured for both total cholesterol and phospholipids; hence, in this fraction, the total cholesterol/phospholipid molar ratio is unaffected by hyperthyroidism. The liver mitochondrial phospholipid composition, unlike the microsomal composition, is altered significantly in hyperthyroid rats; a 7.4% phosphatidylcholine decrease is accompanied by a similar additive percentage increase of both phosphatidylethanolamine and cardiolipin. In regard to total phospholipid fatty acid composition in liver microsomes from hyperthyroid rats, no variation has been observed compared with the control rats, whereas in mitochondria from the same animals, a meaningful linoleic acid decrease with a similar arachidonic acid increase has been found. In addition to fatty acid alteration, the separated mitochondrial phospholipid classes also exhibit some increase in stearic acid. Among phospholipids, cardiolipin changes the most of the esterified fatty acids in hyperthyroid rat liver. In this compound, a strong increase in the percentage of both palmitic and stearic acid and a 32.4% decrease of linoleic acid have been found.     

Correlation between digital differential voltage contrast and infrared microscopy analysis of latch-up in CMOS

Results of latch-up analysis obtained by scanning electron microscopy voltage contrast and infrared (IR) microscopy are correlated and discussed. Voltage contrast detects surface potential changes due to latch-up firing, while IR microscopy reveals recombination radiation emitted by silicon (Si) regions where current density is maximum. Voltage contrast analysis may be difficult in very large-scale integrated (VLSI) circuits because well and substrate regions can be masked by overlying conductors. On the contrary, thanks to the transparency of Si to IR radiation, IR microscopy can detect latch-up by observing the reverse of the device and is not limited by a high metal density.     

IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease

IL-12 has been shown to be involved in the pathogenesis of Th1-mediated autoimmune diseases, but its role in antibody-mediated autoimmune pathologies is still unclear. We investigated the effects of exogenous and endogenous IL-12 in experimental autoimmune myasthenia gravis (EAMG). EAMG is an animal model for myasthenia gravis, a T cell-dependent, autoantibody-mediated disorder of neuromuscular transmission caused by antibodies to the muscle nicotinic acetylcholine receptor (AChR). Administration of IL-12 with Torpedo AChR (ToAChR) to C57BL/6 (B6) mice resulted in increased ToAChR-specific IFN-gamma production and increased anti-ToAChR IgG2a serum antibodies compared with B6 mice primed with ToAChR alone. These changes were associated with earlier and greater neurophysiological evidence of EAMG in the IL-12-treated mice, and reduced numbers of AChR. By contrast, when IL-12-deficient mice were immunized with ToAChR, ToAChR-specific Th1 cells and anti-ToAChR IgG2a serum antibodies were reduced compared to ToAChR-primed normal B6 mice, and the IL-12-deficient mice showed almost no neurophysiological evidence of EAMG and less reduction in AChR. These results indicate an important role of IL-12 in the induction of an antibody-mediated autoimmune disease, suggest that Th1-dependent complement-fixing IgG2a anti-AChR antibodies are involved in the pathogenesis of EAMG, and help to account for the lack of correlation between anti-AChR levels and clinical disease seen in many earlier studies.