Alcap Delivery Devices and the Sustained Release of Difluoronethylornithine (DFNO) in Vitro and in Vivo Using Male Rats

A total of 25 Sprague-Dawley albino male rats were assigned to five groups, each group consisting of five rats. Polylactic acid-impregnated ALCAP capsules filled with 40 mg DFMO were implanted subcutaneously (sc) or intraperitoneally (ip) in group I and II rats, respectively. Rats in group III were implanted with empty ALCAP capsules (ALCAP control). Group IV rats were administered orally 3% DFMO in drinking water. Rats in group V served as control. Blood samples were collected every week for six weeks via the tail artery. The concentration of DFMO was determined by a modified ninhydrin hydrindantin method. Data obtained in this investigation showed that the levels of DFMO in the serum of rats in groups I and II were 41.87 +/- 6.8 and 237.62 +/- 13.3 micrograms/mL, respectively. Body, spleen, liver, prostate, seminal vesicles, and testicular weights of the controls and DFMO treated rats were not significantly different (p less than 0.05) over the entire duration of this study. The diarrhea often noted in rats treated orally with DFMO was not observed in rats implanted with ALCAP capsules filled with DFMO. The results of this study suggest that (1) polymer-impregnated ALCAP ceramic capsules can be used to deliver DFMO in a sustained manner for long durations of time, (2) side effects associated with oral administration of DFMO can be avoided by using DFMO-filled ALCAP ceramic implants, and (3) a ceramic system can be designed to deliver DFMO and drugs such as DFMO in a sustained manner over long periods of time in humans.

The aim of this study was to explore the promoting effect of rosuvastatin on the osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis through the Wnt/β-catenin signal. A total of 30 rats were purchased from the Animal Research Center of Shanxi Medical University. All rats were randomly allocated into three groups, including: group A (control group, n=10), group B (ovariectomized group, n=10), and group C (rosuvastatin gavage group, n=10). The bone metabolism indexes, bone mineral density (BMD) and the Wnt/β-catenin signaling pathway-related proteins in blood samples of rats in each group were measured, respectively. Furthermore, the bone marrow mesenchymal stem cells of rats were used for alkaline phosphatase (ALP) staining. All data were analyzed using the Statistical Product and Service Solutions (SPSS) 22.0 software (IBM Corp., Armonk, NY, USA). The rats firstly received 9 consecutive weeks of feeding with drug intervention. The imaging results revealed that trabecular thickness in group A was significantly higher than that of group B and group C, showing statistically significant differences (p<0.05). After 9 consecutive weeks of feeding with drug intervention, BMD of the femurs of rats in group A and group C was significantly higher than that of group B, showing statistically significant differences (p<0.05). However, there was no significant difference in BMD between group A and group C (p>0.05). The level of calcium representing bone absorption level in serum of rats in group B was remarkably higher than that of group A, and the difference was statistically significant (p<0.05). However, the level of ALP representing bone absorption level in the serum of rats in group B was significantly lower than that of group A (p<0.05). No significant differences were found in the levels of calcium and ALP that represented bone absorption level between group C and group A (p>0.05). Meanwhile. the levels of phosphorus in the three groups were similar, showing no statistically significant difference (p>0.05). Moreover, the expression of ALP-positive cells in the rats of group A and group C was markedly higher than that of group B (p<0.05). After drug intervention through feeding for 9 consecutive weeks, no evident difference was found in the relative expression of Wnt/β-catenin signaling pathway-related protein glycogen synthase kinase-3β (GSK-3β) among the three groups. The relative expression of the protein phosphorylated GSK-3β (p-GSK-3β) in group C was significantly lower than that of group B (p<0.05). Furthermore, the relative protein expressions of β-catenin and cyclin D1 in group C were significantly higher than those in group B (p<0.05). Rosuvastatin can improve bone metabolism in osteoporosis rats and increasing BMD of bone tissues in rats with osteoporosis. Besides, the Wnt/β-catenin signaling pathway plays a crucial role in the regulation of the stem cell self-renewal and bone genesis.

This paper presents a novel topology based on Differential Power Processing (DPP) for feeding solar power into a DC micro-grid. For a PV-to-Isolated Port bus DPP topology, the voltage of the isolated port may fluctuate beyond permissible limits. The voltage level of the isolated port falls below or goes above the reference voltage due to supply or absorption of large mismatched currents, respectively by the DPP converters, in case of significant partial shading for a long duration of time. The proposed topology solves this problem using a bi-directional two-switch flyback converter between the isolated port and the string voltage bus which facilitates exchange of power between them. The development of the proposed architecture from a PV to Isolated port bus DPP topology is discussed. The system has been designed and modelled for ten PV panels. Detailed simulation results have been presented to validate the proposed architecture which show that the two-switch flyback converter maintains the voltage of the isolated port within desirable levels when it is discharged or overcharged due to mismatch between the panels for a long duration of time.

Background: Ikat weavers work manually and non-stop for a long duration of time, which increases the risk of occupational diseases such as musculoskeletal disorders (MSDs). Ikat weaving craftsmen perform work manually and non-stop for a long duration of time which generates occupational diseases such as musculoskeletal disorders (MSDs). This study aimed to determine the analysis of complaints of musculoskeletal disorders (MSDs) among ikat weavers in Langa Bajawa. Subjects and Method: A cross-sectional study were conducted from August to September 2022 among ikat weaving craftsmen in Langa Bajawa region, Ngada, East Nusa Tenggara. A total of 38 subjects were included in this study. The dependent variable was complaints of musculoskeletal disorders (MSDs). The independent variables were age, working period, duration of work, body posture, workload, repetitive activity, stretching, and back rest. The data were collected with study questionnaires, Nordic Body Map questionnaires, Rapid Upper Limb Assessment (RULA) ques-tionnaires, and obser¬vations. The data were analyzed using Chi-square. Results: Age &gt;35 years (OR= 1.07; 95% CI= 1.07 to 17.79; p= 0.034), working period &gt;10 years (OR= 3.85; 95% CI= 0.98 to 15.12; p= 0.049), posture with RULA score &gt;4 (OR= 5.66; 95% CI= 1.36 to 23.46; p= 0.013), working hours &gt;8 hours/day (OR= 10.5; 95% CI= 2.16 to 51.42; p= 0.002), repetitive activity (OR= 11.55; 95% CI= 2.41 to 55.39; p= 0.001), rarely stretching (OR= 0.04; 95% CI= 0.00 to 0.27; p&lt; 0.001), and not having a backrest (OR= 0.09; 95% CI= 0.02 to 0.44; p= 0.001) had a significant effect on complaints of musculoskeletal disorder in ikat weaving craftsmen. Meanwhile, the workload of a person who has a pulse of (&gt; 125 BPM) affected the complaints of MSDs, however, it was statistically insignificant. Conclusion: Age &gt;35 years, working period &gt;10 years, posture with a RULA score of &gt;4, working hours &gt;8 hours/ day, repetitive activities, rarely stretching, not having a backrest, and the work¬load of a person with a pulse rate (&gt; 125 BPM) affect complaints of musculoskeletal disorder in ikat weaving craftsmen. Keywords: complaints of musculoskeletal disorders, craftsmen, ikat weaving.

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;There are numerous publically available smart phone applications designed to track the speed and position of the user. By accessing the phones built in GPS receivers, these applications record the position over time of the phone and report the record on the phone itself, and typically on the application’s website. These applications range in cost from free to a few dollars, with some, that advertise greater functionality, costing significantly higher. This paper examines the reliability of the data reported through these applications, and the potential for these applications to be useful in certain conditions where monitoring and recording vehicle or pedestrian movement is needed. To analyze the reliability of the applications, three of the more popular and widely used tracking programs were downloaded to three different smart phones to represent a good spectrum of operating platforms. Several tests were conducted to evaluate the applications ability to measure speed, elevation change, and positioning on aerial imagery. The data reported by the applications in each test was compared to a Race Logic VBOX VB20SL3 Data Acquisition Unit that was also used in the same tests. The VBOX unit was used as a standard against which to measure the applications efficacy since this unit is specifically designed to monitor and record vehicle movement&lt;span class="xref"&gt;1&lt;/span&gt;. The results show that under certain conditions, speed, positioning on aerial imagery, and elevation change as recorded by applications were relatively accurate for conditions where the recorded period occurred over a long duration of time. The results from this testing shows that recording the motion of a vehicle or pedestrian over a long duration of time, greater than 10 seconds, with minimal changes in velocity can be properly documented by the use of a smart phone running a commonly available applications.&lt;/div&gt;&lt;/div&gt;

Objective: To assess the outcome and complications of plasmapharesis in treatment of myasthenia gravis and factors linked to poor outcome at hematology unit of a tertiary care teaching hospital of Pakistan&#x0D; Study Design: Prospective comparative study.&#x0D; Place and Duration of Study: Pak Emirates Military Hospital/Armed Forces Institute of Pathology, Rawalpindi, from Jan 2018 to Jul 2019.&#x0D; Methodology: A prospective study was conducted on patients of myasthenia gravis presented at our neurology department. All the complications of the procedure were recorded. Outcomes included recovery, shifting to intensive care unit and death. Pearson chi-square was applied to relate the factors with presence of complications or poor outcome.&#x0D; Results: Hypotension 3 (6%) was the commonest complication faced by the patients followed by chest discomfort 2 (4%) during or after the plasmapharesis. Out of 50 patients, 47 (94%) recovered, 8 (16%) had minor complications, 2 (4%) were shifted to the intensive care unit and 1 (2%) died. Long duration of time between onset of symptoms and first session of plasmapharesis had a significant relationship (p-value &lt;0.05) with presence of complications or poor outcome among the patients of myasthenia gravis undergoing plasmapharesis.&#x0D; Conclusion: Plasmapharesis emerged as effective treatment for this immune based neurological disorder with limited side effects. A neurologist should be aware of these common minor and rare major side effects and pay special attention to the patients with generalized myasthenia gravis and those with long duration of time between onset of symptoms and first session of plasmapharesis.Keywords: ,.

This study examines the activities of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) in the liver of 30 adult Wistar rats exposed to nutmeg for 30 days. 1 g of nutmeg was administered to group A (n=10), 2 g of nutmeg to group B (n=10) and group C (n=10) was used as the control. Enzyme activities were assayed in both serum and liver (tissue homogenate) spectrophotometrically. Results obtained showed a significant increase (p &lt; 0.05) in level of AST in serum of rats in group A and B (20.2±7.29 and 23.2 ± 3.27 U/L) when compared to the control group (14.8± 1.78 U/L) while serum ALT level was significantly reduced (5.2± 1.78 and 4.2 ± 0.04 U/L) compared to the control group (7.0 ± 2.6 U/L) but the differences based on dosage was statistically insignificant (p≥ 0.05). The enzyme activities in liver tissue homogenate showed a significant increase (p˂ 0.05) in AST levels (13.8 ± 1.14, 14.6 ± 1.78 and 12.8 ± 0.08 U/L) among test groups and between controls but ALT levels though lower in treated groups than control, was statistically insignificant (p≥ 0.05) among test and between control group (4.6 ± 1.34, 4.0 ± 0.08 and 5.8 ± 0.03 U/L). Differences in enzyme activities due to nutmeg administration may lead to hepatocellular injury as well as myocardial infarction. The results suggests that dosage and long-term consumption of nutmeg could have severe health implication as it affects liver function as well as other associated organ of the body.

Traditional therapies need high systematic dosages that not only destroys cancerous cells but also healthy cells. To overcome this problem recent advancement in nanotechnology specifically in nanomaterials has been extensively done for various biological applications, such as targeted drug delivery. Nanotechnology, as a frontier science, has the potential to break down all the obstacles to be more effective and secure drug delivery system. It is possible to develop nanopolymer based drug carrier that can target drugs with extreme accuracy. Polymers can advance drug delivery technologies by allowing controlled release of therapeutic drugs in stable amounts over long duration of time. For controlled drug delivery, biodegradable synthetic polymers have various benefits over non-biodegradable polymers. Biodegradable polymer either are less toxic or non-toxic. Polylactic Acid (PLA) is one of the most remarkable amphipathic polymers which make it one of the most suitable materials for polymeric micelles. Amphiphilic nanomaterial, such as Polyethylene Glycol (PEG), is one of the most promising carrier for tumor targeting. PLA-PEG as a copolymer has been generally utilized as drug delivery system for the various types of cancer. Chemotherapeutic drugs are stacked into PLA-PEG copolymer and as a result their duration time delays, hence medications arrive at specific tumor site.

Afterglow materials have attracted much attention for medical applications and energy storages due to its individual character. These materials are able to be stored energy during irradiation of the excitation light, and then shows a lasting of the luminescence after turning off the excitation light. SrAl2O4:Eu2+, Dy3+ is one of the famous afterglow material which emits green luminescence and has long duration time. A lot of green and blue afterglow materials such as aluminates and silicates have been reported, but there are few reports of red color afterglow materials with superior property. Y2O3:Eu3+ is one of the famous phosphors having red bright luminescence. However, it doesn’t have afterglow property. D. R. Evans et al.1 reported that Ca2+ co-doped Y2O3:Eu3+ had short duration time with a few minutes after cathode-ray excitation. Also, Y. Lin et al. 2 reported that the afterglow in Mg2+ co-doped Y2O3:Eu3+ had longer duration time with several tens of minutes. Among these materials, entity of oxygen vacancy is a key of afterglow showing. However, previous reports have not explained the difference in the role of each co-doped ion effect to duration time in luminescent materials. Therefore, we focused on the origin of afterglow property in co-doped luminescent materials with oxygen vacancy. We chose R 3GaO6 (R = rare earth elements) phosphor instead of Y2O3-based materials. Eu3+ or Tb3+ doped R 3GaO6 phosphor with bright photoluminescence were already reported.3 As for the electronic structure, top of the valence band and bottom of the conduction band are composed O2p and Y5d, respectively.4 On the other hand, the difference in the crystal structures of Y2O3 and Y3GaO6 gives different number of the oxygen sites. Multi-oxygen vacancy can prepare the multi-energy trap level in R 3GaO6 materials. For this reason, R 3GaO6 phosphors with co-doped ions may show afterglow property. In this study, we prepared co-doped R 3GaO6and investigated relationship between afterglow property and effect of Mg ions. R 2.99-x GaO6-δ :Eu0.01, Ax (R=Y, Gd, A=Mg, Ca, Sr, x = 0 - 0.05) were prepared by solid state reaction using R 2O3, Ga2O3, Eu(NO3)3 and A(NO3)2. All starting materials were mixed with ethanol and sintered at 1723 K for 12 h in air. Powder X-ray diffraction measurement were carried out using Cu Kα radiation (Rigaku, RINT). Emission and excitation properties were measured by spectrofluorometer (JASCO, FP-6500). Afterglow properties were measured after irradiation by handy type UV-light for 10 min. Thermoluminescence measurement (80-600 K) were recorded at 614 nm, which is the emission peak, by changing heating rate (10-50 K/min) in order to estimate the trap depth. R 3GaO6 structure without any secondary phases was obtained in all products and red luminescence was observed during irradiation of UV-light (254 nm) by human eyes. Excitation spectrum showed broad absorption band centered at around 250 nm. This result agrees with reported spectra, indicating observed spectrum is originated from Eu-O charge transfer. 3 Emission spectra showed that red color luminescence is originated from 5D0 - 7Fj (j=1-4) transition, which corroborates the valence of Eu3+. 614 nm emission spectrum was assigned to 5D0 - 7F2 transition. All emission and excitation spectra showed the same shape, and the intensity of those were enhanced by co-doping of A ions. And furthermore, all co-doped products showed the afterglow. The duration times were over 10 min for all products, especially Mg2+ co-doped products had longer duration time than that of Ca2+ and Sr2+ ions. The glow curve obtained by thermoluminescence showed the three peaks in Ca2+, Sr2+ co-doped products. On the other hand, four peaks were observed in Mg2+ co-doped product. The number of peaks corresponds to that of trap levels. Excited electrons transfer from conduction band to trap levels, they can travel to couples of trap levels, and finally go to luminescent center. Therefore, we suggest that the increase in the number of trap levels should lead to longer duration time. The increase in the number of trap levels in Mg co-doped product should be related possibly to the ionic radius. Since ionic radius of Mg ion is smaller than that of R ions, Mg ions cannot stay at the center of original Rionic position. Mg ions in the off-center may form defect pair with oxygen vacancy, resulting a new trap levels. 1. D. R. Evans et al., J. Soc. Inform. Disp., 3, 197 (1996) 2. Y. Lin. et al., J. Alloys Compd., 361, 92 (2003)3. P. Guo. et al., J. Electrochem. Soc., 150, H201 (2003) 4. A. Jain et al., APL Materials, 1, 011002 (2013)

This paper describes our approach to enable Gandalf VMM (Virtual Machine Monitor) to be interruptible. Although Gandalf is shown to be a lightweight VMM, the detailed performance analysis using PMC (Performance Monitoring Counters) showed Gandalf executes with interrupts disabled for a rather long duration of time. By making Gandalf interruptible, we are able to make VMM based systems more suitable for embedded and ubiquitous systems. We analyzed the requirements to make Gandalf interruptible, designed and implemented the mechanisms to realize it. The experimental results shows that making Gandalf interruptible significantly reduces a duration of execution time with interrupts disabled while it does not impact the performance.

BackgroundHepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer.MethodsThirty-two male rats were divided into four groups of eight each as follows, Group A: untreated control; Group B: DEN control (180 mg/kg bw), Group C: DEN + ADE 0.5 g/kg bw; and Group D: DEN +1.0 g/kg bw. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating histological, biochemical, antioxidant enzyme status, cytokines and gene expression profiles.ResultsDEN treatment Groups (B, C, D) showed histological features of HCC and in rats treated with ADE (Groups C, D) partial to complete reversal of normal liver architecture was observed. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), glutatione peroxidase (GPx) and catalase (CAT) were increased, while the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β,, GM-CSF) were increased in the serum of rats in Group B while the anti-tumor cytokines (IL-2, IL-12) were increased in ADE treated Groups (C, D). In addition, Alpha-Feto Protein (AFP) and IL-6 gene expression levels were upregulated in Group B, while they were significantly downregulated in ADE treated Groups (C, D).ConclusionsADE helped in the reversal of DEN damaged liver towards normal. Restoration of anti-oxidant enzymes, liver enzymes, cytokines balance and gene expression to normal levels following ADE treatment indicates that ADE improves liver function and inhibits HCC. ADE can, therefore, be used together with conventional therapeutics for HCC.

Chapter 66 - Symmetrical and Asymmetrical Triazine Herbicides

Chapter 79 - Symmetrical Triazine Herbicides: A Review of Regulatory Toxicity Endpoints

Objective:Since anticancer drugs are to be administered for long durations of time and are associated with systemic toxicities, the present studies were conducted to evaluate the protective potential of honey bee propolis against a widely used anticancer drug, doxorubicin (DXR) induced toxicity and oxidative damage in liver tissues of rats.Materials and Methods:Sixteen male Sprague Dawley rats, weighing between 200-220 g, were used and were divided into four equal groups. Propolis was given orally to rats [250 mg/kg body weight (bw) for 14 consecutive days] and DXR [25 mg/kg bw; intraperitoneally (i.p) was administered on 12th, 13th and 14th day of the experiment. All the animals were sacrificed on day 15th day by decapitation. Blood and tissue samples were collected for measurement of toxicity and oxidative damage parameters (enzymatic assays and biochemical estimations).Results:Administration of DXR for 3 days at a cumulative dose of 25 mg/kg bw, induced toxicity and oxidative stress in rats as significantly decreased activity of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were observed in rat liver supernatants when compared to control group. Increased activity of serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) was obtained in DXR administered rats. Also there are significantly increased levels of lipid peroxides (measured as malondialdehyde formation) and significantly decreased level of glutathione (GSH) in doxorubicin treated rat liver supernatants as compared to healthy controls. On the other hand, administration of animals with propolis prior to DXR treatment led to significant modulation of the oxidative damage related parameters in liver and hepatotoxicity parameters in blood, when compared to doxorubicin treated group. However results were still not comparable to control group or only propolis group indicating partial protection by propolis at the concentration used against anticancer drug toxicity.Conclusion:Propolis extract was found to have a protective effect against doxorubicin-induced toxicity in rat liver though it was still not normalized. It can be concluded that propolis provides partial protection from toxicity of anticancer drug.

Time out from positive reinforcement was examined over a long period of time in a severely autistic child. The child was exposed to three different durations of time out, i.e., 3 min., 1 hr., and 15 min. This child's behavior was best suppressed with the variable 15-min. duration. However, the pitfalls of arbitrarily setting a duration of time out for a child without assessing the effect on him are examined. In addition, the uselessness of group experiments and the problems inherent in long durations of time out are discussed.