Diffusion Theory for the Infection Pathway of Virus in a Living Cell

Background: The infection pathway of virus in living cell is of interest from the viewpoint of the physics of diffusion. Objective: Here, recent developments about a diffusion theory for the infection pathway of an adeno-associated virus in cytoplasm of a living HeLa cell are reported. Theories and Results: Generalizing fractional kinetics successfully modeling anomalous diffusion, a theory for describing the infection pathway of the virus over the cytoplasm is presented. The statistical property of the fluctuations of the anomalous-diffusion exponent is also discussed based on a maximum-entropy-principle approach. In addition, an issue regarding the continuum limit of the entropy introduced in the approach is carefully examined. The theory is found to imply that the motion of the virus may obey a scaling law.

Innovations in Pain Management: Morphine Combined with Omega-3 Fatty Acids

The treatment of acute and chronic severe pain remains a common major challenge faced by clinicians working with the general population, and even after the application of recent advances to treatments, there may still continue to be manifestations of adverse effects.Chronic pain affects the personal and social life of the patient, and often also their families. In some cases, after an acute pain the patient continues to experience chronic pain, which can be a result of diseases such as cancer.Morphine is recommended as the first choice opioid in the treatment of moderate to severe acute and chronic pain. However, the development of adverse effects and tolerance to the analgesic effects of morphine often leads to treatment discontinuation.The present work reviews the different pharmaceutical innovations reported concerning the use of morphine. First, its utilization as the first medication for the treatment of moderate to severe cancer pain and non-cancer pain in patients is evaluated, taking into account the most common complications and adverse effects. Next, strategies utilized to manage these side effects are considered, and we also summarize results using omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) as a monotherapy or as an adjunct to morphine in the treatment of pain.

Enzyme Catalyzed Decomposition of 4-Hydroxycyclophosphamide

According to general doctrine [1] canceroselectivity of Cyclophosphamide is based on different activities of the 4-hydroxycyclophosphamide (OHCP) detoxifying cellular enzyme aldehyde dehydrogenase in tumor and normal cells. Aldehyde dehydrogenase converts the OHCP tautomere aldophosphamide (ALDO) to the non-cytotoxic carboxyphosphamide. Due to different activities of the detoxifying enzyme more cytotoxic phosporamide mustard (PAM) is spontaneously released from OHCP/ALDO in tumor cells. PAM unfolds its cytotoxic activity by forming intrastrand and interstrand DNA crosslinks. This hypothesis is supported by in vitro experiments which show inverse correlations of aldehyde dehydrogenase activity and sensitivity of tumor cells against activated congeners of cyclophosphamide like mafosfamide which hydrolyses within a few minutes to OHCP. In protein free rat serum ultrafiltrate however free OHCP and its coexisting tautomer ALDO are stable compounds. Its half-life in protein free rat serum ultrafiltrate (pH7, 37oC) is more than 20 h. Contrary to protein free ultrafiltrate in whole serum ALDO is enzymatically decomposed to PAM and 3-hydroxypropionaldehyde (HPA) within minutes. The decomposing enzyme was identified as 3´-5´ phosphodiesterase, the Michaelis constant was determined to be 10-3M in human serum.The experiments presented clearly demonstrate that ALDO is not only cleaved base catalyzed yielding acrolein and PAM [2, 3] but also cleaved enzymatically by serum phosphodiesterases yielding HPA and PAM. It is discussed that the reason of the high canceroselectivity of cyclophosphamide is not only due to enrichment of OHCP/ALDO in tumor cells due to less detoxification of ALDO in tumor cells than in normal cells. It is discussed that there is a good reason for an additional mechanism namely the amplification of apoptosis of PAM damaged cells by HPA.A two step mechanism for the mechanism of action of OHCP/ALDO is discussed. During the first step, the DNA is damaged by alkylation by PAM. During the second step the cell containing damaged DNA is eliminated by apoptosis, supported by HPA.

Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

Activated Salivary MMP-2 - A Potential Breast Cancer Marker

It has been reported that Matrixmetalloproteinase-2 (MMP-2) is involved in the pathogenesis of cancer. The over expression of MMP-2 is associated with the progression of malignancy of several types of carcinoma. Human saliva is a biological fluid with several advantages for non-invasive diagnosis and prognosis of diseases. The aim of this study was to detect MMPs expression and activity in biological fluids (saliva, urine etc.) derived from breast cancer patients. Here, our results showed that the activity of MMP-2 was higher at the time before the surgery than after the saliva collected from the same patients. Therefore, we suggested that the highly active form of MMP-2 presented in saliva could be used as a novel potential biomarker for non-invasive diagnosis of breast cancer.

Corrosion Processes Relevant to the Integrity of Oil and Gas Facilities1

The Petroleum Safety Authority (PSA) Norway will set the terms for and follow up that players in the Norwegian petroleum industry maintain a high level of health, safety and the environment and emergency preparedness, and thereby contribute to creating the highest possible value for society. Ensuring good material selection process and structural integrity is an important effort where different corrosion forms are of concern and corrosion protection measures of interest, especially in respect to major accidents.PSA addresses corrosion in rules and regulations, requiring “robust material selection”, with reference to international standards and guidelines. The operators addressing and monitoring of the corrosion effects on the process and structural integrity by incident reporting, reviews and site audits are the key tools for PSA in assessing the corrosion challenges and control in the industry.It is of paramount importance to avoid major accidents. The subject of this paper is to address the challenges with material degradation in ageing structures, and the challenges associated with life extension considerations. Corrosion plays a major role in this respect; especially PSA is concerned with corrosion under insulation (CUI). This paper presents some of our work in these areas.

Computer Aided Formulation and Characterization of Propranolol Hcl Buccal Tablet Using Polymeric Blend

The current study was aimed to formulate a continuous release mucoadhesive buccal tablet containing propranolol HCl. The type and quantities of polymers as well as method of compression were set in a preliminary study (F1-F13). Direct compression method was employed in the main study (F14-F24) using Carbopol® 934P (CP), ethylcellulose (EC), sodium alginate (SA), hydroxypropyl methylcellulose (HPMC k4M) and carboxymethylcellulose (CMC) as mucoadhesive polymers and were tested for physicochemical tests i.e. swellability, surface pH, mucoadhesive time, mucoadhesive strength, in vitro release etc. Results obtained from the study were optimized using NeuralPower® 3.1, an artificial intelligence approach. Against the desirability of physico-chemical parameters, the software optimized the ingredients as HPMC (150mg), CMC (25mg), CP (20mg) and EC (20mg). Outcome revealed that HPMC primarily contributed to the physicochemical properties of mucoadhesive formulation. To compare prediction, optimized ingredients were formulated (F25) and tested. The swellability index of confirmation formulation (F25) was 102% at 6 h. As predicted, similar release pattern was of F25 was obtained as 26% (0.5h), 34% (1h), 40% (2h), 45% (3h), 50% (4h), 62% (5h), 76% (6h), 85% (7h) and 97% (8h) respectively. For release kinetics, DD solver® suggested the release of the drug to be non-Fickian.