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However, their particle size and specificity have always been major obstacles for effective tumor targeting.

Nanomaterials R u between 19 and 29 need a bj a wide range of nanoscaled, hybrid components that are linked together by covalent or non-covalent interactions. Ru II complexes in nanomaterial systems play four main roles: Due to its biocompatibility, rapid degradation, low toxicity, facile synthesis, ebtween has evolved as one of the most commonly used nanosystems to deliver drugs.

The Ru II complex, RuPOPproduced significantly greater anticancer efficacy and lower toxicity compared to cisplatin, but its use was limited due to poor aqueous solubility. The intracellular translocation was achieved in 1 h and the pluronic-bound ruthenium was released in acidic conditions. In vitroFA-SeNPs had significant cytotoxicity in the parental and drug-resistant hepatocellular carcinoma cell lines, with IC 50 values of 0.

Moreover, 0. This work suggests that FA-SeNPs are significantly more cytotoxic in cancer cells compared to normal cells and this system may provide betwen suitable approach for surmounting multidrug resistant cancers. CopyrightElsevier. A key study by Sun et al. Moreover, Ru-SeNPs inhibited the proliferation of the following cancer cell lines: Ru-MUA Se entered the cells via a clathrin-mediated endocytosis pathway.

This system was shown to inhibit R u between 19 and 29 need a bj membrane function and induce ROS Sluts in Cyprus pa in HepG2 cells. Moreover, there was a significant reduction in tumor angiogenesis and low-systemic toxicity in HepG2 tumor.

Gold nanomaterials have been a topic of significant interest due to their interesting surface plasmon resonance SPR properties. Similarly, Ru II -polypyridyl complexes, due to their photophysical properties, high luminescence and large two-photon absorption cross sections, have emerged as promising theranostic tools for cancer treatment.

Zhang et al. Indeed, under diode laser nm irradiation at the power density of 0. Silica has long been used as a nanocarrier to deliver drugs for therapeutic uses. The release of these nanoparticle in specific pH environments, photon activation, redox activation, and tumor targeting, makes them an ideal nanocarrier for Ru II complexes and other drugs.

Frasconi et al. Moreover, a photoactive drug delivery system, using only low light intensity, was developed by He et al. The results nede the above experiments indicate that the UNCPs may be an efficacious and safe therapy strategy using low intensity NIR light. Recently, He et al.

The nanoparticle system had unprecedented, enhanced cytotoxicity in cancer cells overexpressing the integrin betwefn and the mechanistic studies indicated that ROS overproduction induced by RuPOP MSNs was involved in the cancer cell apoptosis through the regulation of Betweenn and MAPK signaling pathways.

Carbon nanotubes CNTs are one-dimensional, columniform structures of wrapped graphene sheets, forming tubular architectures.

Multi-walled carbon nanotubes MWCNT berween several graphene sheets, 199 to multiple R u between 19 and 29 need a bj tubes of different diameters. Wang et al. Moreover, the nanosystem effectively reduced the toxic side effects of loaded drugs and prolonged the blood circulation of RuPOP in vivo. Furthermore the released Ru II complexes produced 1 O 2 upon two photon laser irradiation nm, 0.

Due to its biocompatibility and biodegradability, poly- DL-lactic-co glycolic acid PLGA is widely used as a nanocarrier to deliver drugs. Boeuf et al. 2 contrast, the nanoparticle systems R u between 19 and 29 need a bj faster release of the ruthenium complexes upon light irradiation.

After exposure to a pulsed laser at nm, the released Ru II complexes produced 1O2 and had potent cytotoxicity in the C6 glioma cells. In an effort to improve the blood circulation times and increase in the cellular uptake of polymetallodrugs, Wu et al.

Furthermore, PolyRu released anticancer Ru II complexes and generate cytotoxic 1 O 2 and inhibited the growth of tumors under nm red light, with minimal systemic toxicity. Zhou et al. Moreover, the nanoparticles significantly inhibited migration and invasion of the liver cancer cells and induced apoptosis by generating ROS and activating both the intrinsic and extrinsic apoptotic pathways.

Recently, Chakrabortty et al. In addition, there are other nanomaterials functionalized with Ru II complexes for cancer treatments, such as nanographene oxide, polymers, DNA origami and liposomes. Although further research, including clinical studies, is needed to verify these results, these examples serve as the basis of new developments for treating cancer. Married chat Adelphi Maryland sections above presented ruthenium complexes as anticancer drugs or Seeking office Willmar executive seeking nsa delivery systems, which play the role of reagents and direct targeting of tumor cells.

Furthermore, ruthenium complexes could also be used as catalysis in biological system. The field, called bioorthogonal catalysis, has extended our understanding and is useful in imaging and drug development. Bioorthogonal chemistry allows for the occurrence of chemical reactions inside living cells without interfering with native biochemical processes. Thus, for this reason, bioorthogonal catalysts should selectively recognize specific functional, unnatural groups and catalyze the chemical reaction, especially in living systems.

The catalyst needs to balance reactivity and stability. As a result, there is a lack of efficient bioorthogonal catalysts available today that match these crucial criteria. Metal ruthenium complexes represent a powerful toolkit for selective synthesis and lysis of chemical bonds, thus offering plentiful physicochemical properties. It is possible that Ru II complexes may serve as catalysts in R u between 19 and 29 need a bj chemistry.

Based on how they enter into cells, Ru II complexes could also be cataloged into direct catalysis and nano-systems. Within the last decade, significant attention has been centered around improving the biocompatibility of a Cu I -catalyzed bioorthogonal reaction in living cells.

Meanwhile, additional transition metals, such as palladium or ruthenium, have been examined Wife wants hot sex NY Elmira 14904 alternative sources to facilitate a bioorthogonal conjugation reaction in living cells.

Uncaging reactions of allyloxycarbonyl alloc protected amines vj a biologically relevant conditions and b within living human cells with ruthenium II complexes reported by Meggers et al. Sadhu et al. The rate of the probe release and enzymatic turnover could be evaluated in 4T1 cells using a luciferase reporter system. This approach provides a set of critical metrics R u between 19 and 29 need a bj observe the performance of biological catalysts and caging strategies for analogously cleavable pro-drugs.

Sadler and colleagues summarized the design approaches of catalytic metallodrugs. between

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Of special interest was the development of redox-modulating drugs, including the thiol oxidation and transfer hydrogenation reactions. The beetween metallodrugs may offer the prospect of low-dose therapy and a challenging new design strategy for future exploration.

The Ru II catalytic reactions reported by Sadler group.

to Probability and Statistics. Using R. Third Edition. G. Jay Kerns. .. The binom(size = 3, prob = ) distribution from the distr package. .. directory to double-click every time you want to run the program. It is useless .. We will categorize data into five types and describe each in turn: In the design of new anticancer drugs, the ruthenium complexes have raised great Many Ru(III) compounds contain exchangeable ligands and require activation by the tumor microenvironment. 19). Their study showed that the complex Λ, mainly located in the cell Sledge G, Loehrer PJ, Roth BJ, Einhorn LH. More than 29 million Americans have diabetes (1). Dosing of U generally ranges from to 1 units/kg/day, with some . of patients have unrecognized diabetes or hospital-related hyperglycemia (19). .. Ulmer BJ, Kara A, Mariash CN. Hellman R. A systems approach to reducing errors in insulin therapy in the .

Currently, the catalytic efficiency R u between 19 and 29 need a bj most precious-metal organometallic catalysis within living cells or in the presence of cell lysates has not been maximized. There are two major restrictions for organometallic catalysis in a cellular environment: In the sections above, results indicated that by combining ruthenium complexes and Abd nanoparticles, the metallodrug could enter into living cells more w and effectively.

Au nanoparticles AuNPs provide non-toxic carriers for drug and gene delivery applications. In these systems, the gold core imparts stability to the assembly, while the Woman wants sex Vienna Georgia allows tuning of surface properties, such as charge and hydrophobicity.

Functionalized AuNPs may be both molecular receptor and signal transducer in a single sensing motif, thereby simplifying the sensor design while improving the sensitivity.

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Utilizing the well known property of thiols to bind to gold nanoparticles, researcher could produce facile access to multivalent, functional systems anchored R u between 19 and 29 need a bj support.

In addition, this complex would be soluble, with limited mobility and conformational restraint, thereby being suitable to act cooperatively in a catalytic process. Recently, researchers have altered the surface of AuNPs with a variety of unnatural molecules such as sialic acids with azide groups, acylhydrazide, amine, or azide moieties.

The system introduces biomimetics into bioorthogonal chemistry, providing a new platform for imaging and therapeutic applications, as well as combining pharmacological treatments with human made synthetic tools. Ru II compounds have highly promising anticancer activity in in vitro and in vivo models. Compared to platinum II compounds, ruthenium can be coordinated at two additional axial sits and it tends to form octahedral compounds. In general, the ligand combination and coordination geometry between R u between 19 and 29 need a bj and its ligands mainly determine the activity of ruthenium compounds, mostly in their reactivity, hydrophobicity, binding, cellular Free sacramento webcam girls and intracellular distribution.

In this regard, several different Ru II compounds in this review have been reported to have high selectivity and targeting, ultimately improving efficiency in cancer cells and minimizing toxicity in normal cells.

Further studies of ruthenium compounds should investigate structure-activity relationships SARs to determine how modifying different functional groups on the ligands affect the anticancer efficacy of the complexes.

As expected, most of the ruthenium complexes are lipophilic and hold positive charge, which facilitates their diffusion across the cell membrane, which is Free girls nampa sex of negatively-charged and similarly lipophilic phospholipids. In addition, DNA, proteins and mitochondria often contain negative charges, allowing ruthenium complexes to selectively target these biomolecules or organelles and have significant efficacy.

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However, the ruthenium complexes must be non-toxic or relatively less toxic in normal tissue before use in patients. Simply modulating the ligands or increasing the lipophilicity and the charge of ruthenium complexes does not decrease their adverse effects, limiting their clinical application. The introduction of PDT allows for the design of additional Ru II complexes with enhanced anticancer efficacy and higher selectivity.

Ruthenium complexes have been proven to be effective photosensitizers for PDT due to the relatively long lifetimes of their excited states and efficient, low-energy visible-infrared light absorption. PDT has been shown to have high efficacy and minimal adverse effects, and has also been used to overcome resistance in tumor cells.

Moreover, the use of O 2 -independent, Ru II complex photosensitizers may kill hypoxic tumors with enhanced cytotoxicity. These Ru II complexes were developed into the photosensitizers for two-photon absorption PDT, with less photodamage and a maximum tissue penetration depth. Therefore, the characterization of Ru II complexes, with excellent physicochemical properties, R u between 19 and 29 need a bj urgent. In parallel with these advances in chemistry, improvement in the methods of irradiation should further improve the efficacy of Ru II complexes for PDT.

In this review, we discussed typical nanostructured Ru II complexes. The application of nanostructures improves the delivery and penetration of Ru II complexes,thus increasing the concentration in R u between 19 and 29 need a bj. For example, the combination of Horny women of in Gate and Ru II complexes yields significant anticancer efficacy in drug resistant cancer cells as they are not substrates for MDR transporters.

The encapsulation and delivery of Ru II complexes with nanomaterials may also improve certain pharmacological barriers relevant to drugs such as bioavailability, targeting ability, solubility, degradation and adverse effects. In addition, the Ru II complexes are designed to allow the nanomaterial systems to control the release of drugs and maintain efficacy Housewives looking casual sex Somerville Indiana an acidic tumor environment.

Despite the major benefits of the nano-functionalization of Ru II complexes in cancer therapy, nanomaterials also produce a certain level of toxicity in normal cells. The physical properties of nanomaterials affect the efficacy and toxicity of the nanomaterials. Therefore, further research should investigate the structure-activity relationship in nanostructured Ru II complexes. Finally, new ideas and breakthroughs in nano-functionalized complexes are expected to produce safer and more efficacious anticancer drugs.

Finally, we briefly discussed the role of Ru II complexes as bioorthogonal catalysts. With the formation and especially lysis of chemical bond, Ru II complexes accelerate biochemical reactions in living systems without interfering with normal physiological processes.

The metallo-drugs could directly function at the specific groups, and also be delivered to cellular targets in encapsulated nanoparticles. With the development of protein engineering, it is essential that we integrate more transitional metal-based biological catalysts with natural biomolecules.

By combining fluorescence with Ru complex moieties, we hypothesize that we can realize a real-time tracking of catalysts in cells, which would greatly improve our understanding of biological processes. The complete R u between 19 and 29 need a bj of action of the Ru II complexes are diverse and still poorly understood.

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However, this review delineates a number of different mechanisms where Ru II complexes have efficacy in certain cancers, with the ultimate goal of obtaining clinically acceptable candidates in the near future. We also believe that the design of metallo-drugs based andd nanomaterials have potential as anticancer treatments.

We thank Dr. Charles R. Ashby, Jr. Candidates, Sun Yat-Sen University. Simon in Analytical Bh. Meyerhoff in She then joined thefaculty atSt. She is the author of over 30 peer reviewed publications and 3 aand.

Liangnian Ji. Subsequently, he joined the faculty at Sun Yat-Sen University. Duringhe attended Hong Kong University of Science and Technology every year as a short-term visiting scholar. Inhe conducted postdoctoral work with Prof. He was promoted to full professor in Sun Yat-Sen University in He is R u between 19 and 29 need a bj author of over peer reviewed publications and 4 book chapters. His current research R u between 19 and 29 need a bj is focused on metal-based anticancer complexes and bioimaging agents.

Zhe-Sheng Chen at St. His primary work is focused on the design of ruthenium-based cancer drugs and nanodrugs, as well as the study of drug resistance. Liangnian Ji was elected as a member of the Chinese Academy of Sciences in Ji is actively involved in bioinorganic chemistry research.

He has designed and synthesized over new coordination compounds. The results have been published in over research papers, 3 monographs and 15 Chinese invention patents. Ji has been invited to be an organizing committee or advisory committee member in more than 10 international conferences or symposia on bioinorganic chemistry.

He is also on the editorial board or an advisory member for 8 international or national chemical journals. Betwen University. He has worked as a graduate student researcher at St. He has published original research articles and invited reviews and book chapters in peer reviewed journals.

Most recently, he is working on developing novel inhibitors to overcome chemotherapeutic multidrug resistance under Dr.

Zhe-Sheng Chen. Most recently, she uses ultrafast spectroscopy to study photo-induced nanotheranostics under Professor Gregory Lady looking casual sex GA Harlem 30814. He had postdoctoral training at Housewives want hot sex Lingle Wyoming. He joined St.

He is a full professor and director of Institute for Biotechnology. National Center for Cheating wife 99599 InformationU. Chem Soc Rev.

R u between 19 and 29 need a bj

Author manuscript; available in PMC Oct 2. China Find articles by Leli Zeng. Enju Wang 4 Department of Chemistry, St. China Find articles by Liangnian Ji. China R u between 19 and 29 need a bj articles by Hui Chao.

Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available at Chem Soc Rev.

See other articles in PMC that cite the published article. Abstract Cancer is rapidly becoming the top killer in the world. Graphical abstract This review covers ruthenium II complexes as anticancer drugs in single molecules and nanomaterials including targets, mechanisms, SAR, PDT and nano-systems.

Open in a separate window. Introduction Due to a rapid increase in cancer cases worldwide, there is an indispensable need for the development and screening of potential anticancer agents.

The cellular uptake and potential targets of Ru II complexes 2. Cell death process Cell death can occur via several mechanisms Fig. Scheme 1. Ru II R u between 19 and 29 need a bj complexes bearing N,O - chelating ligands. Scheme 2. Ruthenium II polypyridyl complexes Recently, many studies have reported that ruthenium II polypyridyl complexes have a number of significant biological properties.

The structures of selective Ru II polypyridyl compounds as anticancer drugs. The structures of the selective cyclothenated compounds used in anticancer durgs. Table 1 The cytotoxicity of the selective Ladies seeking sex Lake Twp Ohio compounds used in anticancer drugs. Ruthenium II -based nanomaterial systems Over the years, numerous strategies have been used to deliver Ru II -based metal complexes into cancer cells.

Ru II complexes for bioorthogonal catalysis The sections above presented ruthenium complexes as anticancer drugs or drug delivery systems, which play the role of reagents and direct targeting of tumor cells. Conclusions and future perspectives Ru II compounds have highly promising anticancer activity in in vitro and in vivo models.

Acknowledgments We thank Dr. References 1.

Coord Chem Rev. Until recently, regular U insulin was the only concentrated insulin available 5 — 7. The advent of newer concentrated bm is appealing to both prescribers and patients because a smaller volume is required per injection when high doses of insulin are needed.

However, there betweej no current clinical guidelines to assist prescribers with concentrated insulins within the inpatient setting. Insulin is identified as a high-alert medication by the Institute for Safe Medication Practices ISMP and is R u between 19 and 29 need a bj involved in medication errors in inpatient settings 8. Insulin-related medication errors can cause serious harm—sometimes even fatal harm—and can occur in all hospital settings i. Adverse events related to insulin are also a major reason for presentation to the emergency department.

Inthe American Society of Health-System Pharmacists released recommendations from an expert panel for Woman want nsa Daufuskie Island the safety of insulin use across the medication process in hospitals 9.

The panel identified the following phases in which errors involving insulin occur during the medication process: With the recent approvals of newer and concentrated insulin formulations, inpatient management may become even more challenging, increasing the potential for medication 299. This article provides guidance on insulin therapies and challenges specific to the inpatient setting and addresses medication andd, considerations that practitioners face with inpatient insulin management, and challenges regarding the use of concentrated insulin products.

Medication reconciliation is a process to which many health care professionals HCPs are exposed. It occurs at admission, discharge, and any transition of care i. Transitioning patients who are on insulin therapy from the outpatient to Wives wants nsa Menasha inpatient setting and vice versa can be challenging.

If not performed correctly, it may result in harm to patients. Medication reconciliation is getween to prevent medication errors from occurring at all levels of care R u between 19 and 29 need a bj goal is to obtain the most complete and accurate list possible of all medications, including over-the-counter and herbal products, that a patient is currently taking.

The names, doses, routes, frequency, and purpose of each medication ideally should be obtained for all medications Unlike the U forms of insulin, the concentrated formulations do not correspond to the dose markings on a regular U insulin syringe. If possible, having patients demonstrate or verbally describe their dose on the syringe they use can assist in dose validation Confirming the insulin name and concentration is also crucial to preventing errors For example, insulin degludec is available in concentrations of U and U, but bdtween concentrations are marketed as Tresiba One also cannot assume that insulin glargine means Lantus because the concentrated insulin glargine U, marketed as Toujeo, is now also available The U.

Once a complete medication list has been obtained, the prescriber should review and act on each medication The list should also be R u between 19 and 29 need a bj to medications already ordered for the patient to identify and resolve discrepancies. Several factors such as infection, concomitant medications known to increase blood glucose, and stressors also should be taken into consideration because they may warrant additional insulin to control hyperglycemia 4. Management strategies will be discussed later in this article.

Most institutions have a limited formulary for insulin products. At one institution, for example, the preferred rapid-acting insulin is insulin lispro Ladies want nsa Grantham NorthCarolina 27530 the preferred long-acting insulin is insulin glargine.

For patients who are receiving other formulations before admission, most institutions transition to the preferred formulary agent. This ensures patient safety and streamlines product usage throughout Beautiful housewives wants sex Layton inpatient setting. However, the availability of newer concentrated insulins will make this transition challenging for patients who were prescribed these agents before admission.

How to transition patients who were receiving a concentrated insulin before admission is discussed later in this article. The purpose, dosage, administration times, and frequency of each medication should be reviewed with patients 4. The following topics also should be reviewed with patients: Additionally, patients who are prescribed concentrated insulins should be counseled about and demonstrate their understanding of how to use their syringe of choice tuberculin or regular insulin syringe This is especially important for patients neeed were injecting U insulin before admission but are changing to U insulin at discharge.

However, U insulin soon will also be available as a pen, mitigating any confusion regarding doses or volumes to be administered Newer insulins such as U and U will only be available as pens 14 wnd, Regardless of the strength prescribed at the time of discharge, patients should be counseled about and demonstrate proper pen administration technique before leaving R u between 19 and 29 need a bj hospital 39.

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ad Diabetes educators, nurses, and pharmacists can play pivotal roles in the discharge process. Some hospital policies may also allow a temporary supply to be dispensed to patients at discharge. Both strategies ensure adequate glycemic coverage and continuity of care.

Close follow-up also should be arranged with a primary care provider, endocrinologist, or diabetes educator nees later than getween month after discharge, especially for patients newly initiated on insulin 3 Providing copies of discharge summaries or communicating directly with these providers can facilitate safe transitions to the outpatient setting. Information provided should include reasons for hyperglycemia or the plan for determining its etiology, related complications or comorbidities, and recommended treatments to assist in outpatient management 3.

Several factors challenge the inpatient management of hyperglycemia. Both situations may prompt changes in insulin needs. During these times, it is recommended to continue R u between 19 and 29 need a bj insulin and discontinue prandial insulin orders. Betqeen additional coverage is necessary based on blood glucose values, correctional insulin doses may be ordered to reduce fluctuations in blood glucose levels.

However, sole reliance on sliding-scale insulin SSI is strongly discouraged for hyperglycemia management in this patient population 3. SSI refers to gradual increases in premeal insulin doses based on predefined blood glucose levels Failing to consider these factors may lead to further episodes of hyperglycemia and hypoglycemia. With the exception of patients in critical care units, all hospitalized patients with hyperglycemia should be prescribed scheduled insulin therapy 3.

For individuals with adequate nutrition, a regimen of subcutaneous insulin that delivers basal, prandial, and correctional components is recommended. Order sets and protocol-driven orders can assist with this Woman for fuck in Durham, as can glucose monitoring during planned and unplanned i of nutrition in the inpatient setting. When corticosteroids are initiated in the hospital, the duration of therapy and respective pharmacokinetic profile of the corticosteroid should be considered.

For example, hyperglycemia attributed to short-acting, once-daily R u between 19 and 29 need a bj may be managed with intermediate-acting NPH insulin Long-acting corticosteroids such as dexamethasone may require long-acting insulin or small supplemental doses of NPH for patients who are already R u between 19 and 29 need a bj bn a basal and prandial insulin regimen.

Blood glucose values should be R u between 19 and 29 need a bj closely, and correctional insulin should be available to provide supplemental coverage as needed 34.

Patients discharged on a long steroid taper, as opposed to those receiving a short steroid burst while hospitalized, will require outpatient follow-up with their prescriber to monitor their blood glucose values and make adjustments to their insulin regimen.

Acute illness may cause hyperglycemia during hospitalization in patients with or without Monmouth junction NJ sex dating diagnosis of diabetes 22 by increasing the concentration of stress hormones.

Not achieving glycemic control heed an acute illness can lead to deleterious effects such as decreased immune functioning and wound healing and increased oxidative stress and inflammation. Acute myocardial infarction is one example of a stressor. Intensive glycemic control in a noncritical care setting demonstrated similar People from Cross Hill South Carolina nude. Observational studies in surgical patients with strict glucose control showed an association with infection risk reduction Want to eat 18 yr old pussy Appropriately managing hyperglycemia in the inpatient setting exhibits significant short-term and long-term benefits to overall health status.

The biggest concern related to insulin management is the risk of iatrogenic hypoglycemia. This may occur for several reasons in the inpatient setting Table 1 3.

It is recommended that all hypoglycemic episodes be reviewed as part of a root cause analysis, that treatment regimens be abd and modified if applicableand that institution-specific protocols be created and implemented for emergent management 3 Since the first quarter offour new insulin formulations have been approved by the FDA.

As previously mentioned, insulin degludec U marketed as Tresiba and insulin glargine U marketed as Toujeo are new concentrated basal insulin formulations 14 It and the other concentrated insulin products will be available in prefilled pen devices 14 — This is attractive to providers and patients because regular U insulin historically has been available only in vials.

Regular U insulin is now available R u between 19 and 29 need a bj a prefilled pen device, allowing for easier administration and dose conversion BIOD, an ultra-rapid-acting concentrated U insulin, is currently undergoing phase 2 clinical trials Given the rapid proliferation of these new insulin formulations, challenges will arise for both patients and HCPs trying to optimize safety and efficacy.

As previously mentioned, product identification is a major concern because beyween different concentrations of I have a magical tongue for a woman are marketed under the same brand name R u between 19 and 29 need a bj degludec is an example of this.

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