Functional ordered mesoporous silica in nanomedicine: target and drug delivery systems.

Ordered mesoporous materials (OMMs) are characterized by high surface area (up to 1000 m2/g), high pore volume (1-3 cm3/g) and narrow pore size (2-30 nm) distribution. Recently, mesoporous silica nanoparticles (MSNs), a subclass of OMMs, have had great development as nanocarriers for drug delivery, particularly for cancer treatment. The research activity of my PhD work was aimed to study SBA-15 and MCM-41 mesoporous silica samples for biomedical applications. The texture and the structure of the synthesized materials were characterized through N2 adsorption/desorption isotherms, SAXS, and TEM. The functionalization of the mesoporous silica samples was verified by means of Fourier-transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). DLS and ELS were used to determinate hydrodynamic diameter and zeta potential of the studied systems under different conditions. The PhD thesis focused on different aspects of the use of OMMs, particularly MSNs, as drug nanocarriers. In the first paper how different features of OMMs (surface area, pore size and surface charge) can affect the adsorption and release of drugs was investigated. Ampicillin, a penicillin-like -lactam antibiotic was loaded on MCM-41, SBA-15, and amino-functionalized SBA-15, then its release in simulated physiological conditions was studied. This study demonstrated that to obtain a sustained drug release, the chemical nature of the matrix’s surface plays a role which is more important than its textural features. SBA-15-NH2 matrix is a suitable candidate as depot system for local sustained release of ampicillin. Common target systems have the disadvantage that the targeting molecule can be recognized by several receptors. A possible strategy to solve this issue was investigated in the second paper. The targeting molecule was hidden by preparing a double sequential targeting system. To this purpose a double target system was synthesized. Alendronate was used as a tissue target to recognize a diseased bone, and an encrypted cellular target, Arg-Gly-Asp (RGD) was used to improve the internalization in human osteosarcoma cells (collaboration with Universidad Complutense de Madrid). This preliminary study showed the efficacy of the double target systems. The next step could be the functionalization of MSNs with the previously described systems for the synthesis of a smart target systems usable as a carrier for anticancer drugs against bone cancer. In the third paper, the effect of surface charge on the internalization of MCM-41-type MSNs, functionalized with chitosan (CHIT) and hyaluronic acid (HA) biopolymers, on 3T3 mouse fibroblast cells was then investigated. The opposite surface charge of the biopolymer-functionalized MSNs (negative for MSN-HA and positive for MSN-CHIT) gave a different interaction with BSA, used as a model protein to investigate the formation of the protein corona (forth paper). Finally, in the fifth paper, MSNs were functionalized with HA samples having three different molecular weights (HAS, HAM, and HAL). The effect of HA molecular weight on the internalization of HA-MSNs particles on HeLa cells was evaluated. These last studies showed the importance of the external functionalization on the interaction between MSNs and the components of body fluids, that change their surface properties. These changes as well as the polymer’s features (i.e. the molecular weight) are able to modulate the cellular uptake. The obtained results highlight the importance of the physico-chemical phenomena occurring at the nano-biointerface for the future use of functionalized OMMs and MSNs in nanomedicine. The present findings confirm that these nanocarriers are very promising matrices for the obtainment of targeting drug delivery systems for cancer treatment

Intellectual Property Law - Newcombe v. Adolf Coors Co.

In Newcombe v. Adolf Coors Co., the United States Court of Appeals for the Ninth Circuit held that a Major League baseball pitcher, retired for over thirty years, had valid publicity infringement claims against defendants who created an advertisement using a drawing of his stance. According to the court, a material factual issue existed as to whether the drawing of the stance in the advertisement conjured up images of the pitcher, even though the pitcher\u27s face could not be identified from the drawing, and his name did not appear anywhere in the advertisement. Thus, the court found a subtle image such as a stance may constitute likeness for claims under section 3344(a) of the California Civil Code and common law

How the Holding in Dent v. National Football League Tackles Collective Bargaining Agreements

In 2014, a group of retired professional football players sued the National Football League (“NFL”), claiming that the league distributed con- trolled substances and prescription drugs to them in violation of state and federal laws. The trial court ruled that the players’ state law claims are preempted by section301 of the Labor Management Relations Act (“LMRA”), and that the players should instead follow the arbitration procedures set out in the agreed upon collective bargaining agreement. However, the Ninth Circuit reversed the NFL’s motion to dismiss on the grounds that the players’ claims are not preempted by section 301. Ultimately, the Ninth Circuit Court of Appeals’ ruling in Dent v. National Football League may place the liability of caring for the health and safety of players directly on the NFL itself rather than individual teams. This essentially ignores the policies set out in the collective bargaining agreement. This Comment argues that the Ninth Circuit erroneously reversed the trial court’s ruling, because the claims brought against the NFL by the retired professional football players should be preempted by section 301 of the LMRA. Furthermore, this Comment argues that the Ninth Circuit’s decision interferes with the uniformity of interpretation of collective bargaining agreements. For this reason, the ruling is unfair to not only the league, but to other organizations and companies who also rely on collective bargaining to negotiate with employees

Intellectual Property Law - Newcombe v. Adolf Coors Co.

In Newcombe v. Adolf Coors Co., the United States Court of Appeals for the Ninth Circuit held that a Major League baseball pitcher, retired for over thirty years, had valid publicity infringement claims against defendants who created an advertisement using a drawing of his stance. According to the court, a material factual issue existed as to whether the drawing of the stance in the advertisement conjured up images of the pitcher, even though the pitcher\u27s face could not be identified from the drawing, and his name did not appear anywhere in the advertisement. Thus, the court found a subtle image such as a stance may constitute likeness for claims under section 3344(a) of the California Civil Code and common law

Financial Performance Growth of Oman Cement Company

Purpose: The objectives of the study were to analyze the financial growth of Oman Cement Company (OCC) to critically investigate the financial performance along with its growth in the Oman cement industry. Design/methodology/approach: The data was collected from the five years’ financial statements between 2016 and 2020 listed in the Muscat Security Market and the analysis was carried out applying the different ratios – profitability ratios, liquidity ratios, management efficiency ratios, operating ratios, and financing ratios. Findings: The results of the study reveal that the OCC growing more efficiently in finance with effectively utilizes its assets. The company liquidity position was given a positive sign during the study period. The management and operating efficiency are less, and it needs improvement.  Overall financial growth is stable impartment started during the end of the study period.  Research limitations/implications: The study implies that the company management needs to utilize the fixed assets and improve the cash and cash equivalents. The production policy needs an eye on the future success of management.  Social implications: The study suggests that the management should act wisely in handling finance. Further, the OCC policies should maintain standards to compete with foreign competitors. Originality/Value: Only a very few have examined the causes for the financial issue in the Oman cement industry, and it is a first-hand study of its kind, and the results will be useful to the stakeholders.

Genetics of Tobacco Use

The worldwide prevalence of tobacco use is widespread, resulting in nearly 4.5 million deaths every year. Nicotine is addictive and has psychopharmacological effects that maintain the use of tobacco products. Several studies have documented a strong hereditary component to tobacco use. The present article reviews results from twin and adoption studies and proceeds to present association studies of specific genes that may be involved in tobacco use. Cholinergic receptor nicotinic beta polypeptide 2, serotonin receptor and transporter genes, dopamine receptor and transporter genes, and the cytochrome P450A6 gene are reviewed. Linkage studies help to identify regions of the genome that may be worth further investigation. The paper concludes with a discussion of the limitations of genetic research and the future of genetic epidemiology in this domain

Pharmakokinetik und Metabolismus von Erlotinib nach Single- und Multiple-Dose

Das Pankreaskarzinom zählt zu den bösartigsten Tumorarten. 2005 wurden in Österreich insgesamt 1318 Todesfälle verzeichnet, davon 650 Männer und 688 Frauen. Die Diagnose erfolgt für eine erfolgreiche Therapie meist zu spät. Das liegt vor allem an den uncharakteristischen und sich oft über Monate entwickelnden Symptomen. Die vorliegende Arbeit bietet einen interessanten Überblick über die Konzentrationsverläufe von Erlotinib und seinen Metaboliten OSI-420. Es wurden 100 mg/Tag peroral verabreicht. Es konnte keine Kumulation beobachtet werden, dies ist vor allem bei kontinuierlicher Verabreichung klinisch relevant. Der Hauptmetabolit OSI-420 wird zu rund 2-10 % (bezogen auf die Plasmakonzentration von Erlotinib) gebildet. Die gewonnen Daten stimmen mit der aktuellen Literatur überein und sind somit sehr aussagekräftig. Das bedeutet, dass im Falle der Therapie eines Pankreaskarzinoms keine Änderung der Erlotinib–Pharmakokinetik zu beobachten ist. Weiters ist trotz der geringen Anzahl der Patienten, eine Interaktion mit Arzneistoffen der Prä- oder Co- Medikation nicht erkennbar

Adsorption and release of ampicillin antibiotic from ordered mesoporous silica

In this work the adsorption and the release of ampicillin - a β-lactam penicillin-like antibiotic - from MCM-41, SBA-15, and (amino functionalized) SBA-15-NH2 ordered mesoporous silica (OMS) materials were investigated. The silica matrices differ for their pore size (SBA-15 vs. MCM-41) mainly, and also for surface charge (SBA-15 and MCM-41, vs. SBA-15-NH2). OMS samples were characterized through small-angle X-rays scattering (SAXS), transmission electron microscopy (TEM), N2 adsorption–desorption isotherms, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and potentiometric titrations. The quantification of immobilized and released ampicillin was monitored by mean of UV–Vis spectroscopy. Experimental adsorption isotherms evidenced that ampicillin's loading is not related to the pore size (dBJH) of the adsorbent. Indeed the maximal loadings were 237 mg/g for SBA-15 (dBJH = 6.5 nm), 278 mg/g for MCM-41 (dBJH = 2.2 nm), and 333 mg/g for SBA-15-NH2 (dBJH = 5.6 nm). Loading seems, instead, to be related to the surface charge density (σ) of the sorbent surface. Indeed, at pH 7.4 ampicillin drug is negatively charged and likely prefers to interact with SBA-15-NH2 (σSBA-15-NH2 = +0.223 C m−2) rather than the slightly negatively charged silicas (σSBA-15 = −0.044 C m−2 and σMCM-41 = −0.033 C m−2). Similarly, ampicillin release is affected by interfacial interactions. Indeed, we found a burst release from pure silica samples (SBA-15 and MCM-41), whereas a sustained one from SBA-15-NH2 sample. We explain this behavior as a result of an attractive interaction between the protonated amino group of SBA-15-NH2 and the negatively charged carboxylate group of ampicillin. In summary, in order to obtain a sustained drug release, the chemical nature of the matrix's surface plays a role which is more important than its textural features. SBA-15-NH2 matrix is hence a suitable candidate for local sustained release of antibiotic drugs

Sex i paradiset : Konformitet i samband med sexuell aktivitet

Many university students feel that their sexual activity is either not sufficient or that it is too high. This leads to dishonesty and discomfort concerning the subject when it is discussed. This can be seen as a sign of conformity. The goal of this quantitative study was to explore a possible correlation between conformity and sexual activity in two university programs at Lund University, Sweden. Guided by theories on conformity the study analyzed similarities and differences within the correlation of conformity and sexual activity. Particular attention was paid to differences in gender, relationship status, and faculty. 227 questionnaires were collected and analyzed. The findings show that students overestimate the sexual activity of their peers and therefore create an illusion of a norm, and that 44.5 % of all the respondents do conform when it comes to sexual activity. Ïndividuals that are not in a relationship and individuals that have not had sex conform the most, but in contrast to previous research this study shows that conformity amongst men is higher than amongst women. The results highlight the need for further research within the subject of sexual activity