Abstract: The release of heavy metals in to the aquatic environment causes water pollution problems because of their toxicity, persistence and bioaccumulation. Lead has no known role to play in the human body that is physiologically relevant, and its harmful effects are myriad. Lead from the atmosphere and soil ends up in water bodies thus affecting the aquatic organisms. This situation has thus prompted numerous investigators to study on the effects of this heavy metal on the biological functions of aquatic organisms, particularly on the antioxidant enzyme activity in fish. In the present investigation the effect of lead acetate (heavy metal) on antioxidant enzyme activity was evaluated in the fresh water fish Labeo rohita. The experimental fish were treated with sub lethal concentration of lead acetate (0.015 mg/ L) for 120 hrs. Spirulina was used as supplementary feed during the experimental period. We observed various lead induced lipid peroxidation (LPO), antioxidant enzyme (SOD and CAT) changes and Spirulina supplementary feed therapeutic efficiency was observed in the gill and liver tissues of the fish. All the experimental data are statistically significant at p<0.05% level. The present study was under taken the toxic effect of lead acetate on Labeo rohita fish and chelating property of Spirulina.
subjected to rigorous characterization and its selective cell targeting, ROS generation and PDT efficiency were studied in vitro. Although, UCNs have been deemed safe with no major toxic effects in various reports that performed short term toxicity and biodistribution studies,[22, 23] their long term effects and potential bioaccumulation remain largely unexplored. Hence, before studying the therapeutic effect of these nanoparticles following systemic administration in vivo, its biodistribution and long term (120 d) toxicity profiles were analyzed, to determine a single safe dose for systemic administration in vivo. Lastly, we have also compared the therapeutic efficiency of UCN-based 980 nm NIR PDT, with conventional PS Chlorin e6 (Ce6) excited at 665 nm visible light to highlight the advantage of utilizing NIR light for the control of solid and bulky tumors.
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Background: Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is a fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs. Methods: In vivo study, a total of forty-eight 10-week-old male Sprague-Dawley (SD) rats were used. Twelve rats received intraperitoneal injection of PBS as the sham group; the rest received intraperitoneal injection of 60 mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM group), MSCs (M group), or administrated probucol after intracavernosal injection of MSCs (P + M group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In in vitro experiment, H 2 O 2 was used to create oxidative stress environment to detect
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Newer MRI techniques have been applied to help diagno- sis and prognosis. Diffusion-weighted magnetic resonance (MR) imaging detects the water mobility to reflect the mor- phologic and physiologic changes in tissues which was wildly applied in chest tumors characterization [9, 10]. tThe apparent diffusion coefficient (ADC) of the lesion but these readings have more recently been suggested to have some prognostic value as well as diagnostic in brain metastases cancers [11, 12]. An inverse relationship was observed be- tween ADC values and tumor cellularity . Previous stud- ies had shown that ADC values can be used in differentiating between certain types of cerebral tumors [13–15]. However, the efficiency of the ADC values as an index of brain metastases, and its advantages over MRI re- main controversial.
The H-ras12V mice with liver cancer were randomly divided into four treatment groups containing four mice each, ie, control, Pdcd4, FPCP-Pdcd4, and PEI 25 kDa- Pdcd4. The mice were intravenously injected with 30 µ g of the therapeutic Pdcd4 gene twice per week for four weeks with or without the carrier. The same volume of phosphate-buffered solution was intravenously injected into mice in the control group. At the end of the experi- ment, the mice were sacrificed, the livers were collected, and the numbers and sizes of tumors on the surface were evaluated. The livers were homogenized using 2.5 × Passive Lysis Buffer (Promega), then centrifuged at 13,000 rpm and 4 ° C. The protein concentration from the homogenized liver samples was evaluated using the Bio-Rad Protein Assay reagent (Bio-Rad, Hercules, CA, USA). Western blotting was performed following a procedure described previously. 22 Bands were detected using a luminescent image
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After destroying the physical barriers of the ECM, the therapeutic effects were then studied by transcatheter pro- cedures, which have not been performed before as far as we know, but just Golubnitschaja et al reported that TACE treated patients tending to better survival in situation of lower MMP-9 activities. 35,36 ANOVA analysis revealed that the growth rate of the RLX combined with TACE group was signi ﬁ cantly decreased compared with the TACE and the NS group, however, the necrosis rate was signi ﬁ cantly increased compared with the other two groups. It indicated that RLX combined with TACE pro- cedures for the treatment of VX2 tumor could result in impaired growth that complied with enhanced necrosis. Besides, the TUNEL and Ki67 staining identi ﬁ ed the out- comes through cross-validation. Moreover, the HE stain- ing also presented that a better effect was achieved in the RLX combined with TACE group.
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It is known that the efficiency of pioglitazone is associ- ated with the implementation of good glycemic control and improvement of insulin sensitivity on the one hand; on the other hand it improves dyslipidemia, hypertension and microalbuminuria in patients with T2DM. Some studies have shown that pioglitazone increases the levels of HDL cholesterol and reduces the levels of triglyceride, fasting plasma free fatty acids, without affecting the levels of total cholesterol and LDL cholesterol [34, 35]. As specific ago- nists of the PPAR- γ , TZDs reduce the levels of circulating pro-inflammatory biomarkers of atherosclerosis , more- over, in patients treated with pioglitazone significantly lower rate of progression of coronary atherosclerosis was ob- served . The effect of TZDs was associated with in- creased levels of adiponectin (vascular protective adipokine) and reduced levels of tissue necrosis factor α , which in turn leads to a decreased risk of cardiovascular complications. TZDs exert beneficial effect on coronary and peripheral vasodilation, with minimal improvement of blood pressure. Small controlled studies, using surrogate markers such as the intima-media thickness of the carotid artery, have shown improvements in patients treated with TZDs . Protective effect against restenosis after percu- taneous intervention in TZDs treated patients was also in- dicated [39, 40]. During the Duration-4 trial significant changes in serum lipids were not observed. The decrease in systolic blood pressure were: − 1.3 mmHg (0.8 mmHg), − 1.7 mmHg (1.0 mmHg), and − 1.8 mmHg (1.0 mmHg) in therapy with exenatide, pioglitazone and sita- gliptin, respectively. Reduction in diastolic blood pressure is achieved only on therapy with pioglitazone: − 2.5 mmHg (0.6 mmHg). Compared with other drugs pioglitazone de- creased heart rate .
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R. serpentina is well documented to exhibit potential medical values for treatment of hypertensive and neurological disorders. Extensive research has been carried out exploring its antihypertensive properties; however, limited literature is presently available on its neuropharmacological activities despite it being reported as the first neuroleptic compound. Although it was later reported for many CNS disorders, therefore R. serpentina covering the broad spectrum array of pharmacological activity proves to be an ideal therapeutic target for neurological disorders.
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ABSTRACT: Raise in the multidrug resistance gave challenge to the treatment of tuberculosis with first line medication due to less response. Nanoparticle drug delivery has proven efficiency in improving the therapeutic efficacy of many drugs. Reduction of dosing frequency was achieved by applying drug delivery using Nano medicine and Green Nanotechnology. The present study aimed in the production of such drug conjugates of Isoniazid using interdisciplinary technology of nano medicine and green nanotechnology. Isoniazid Nano- conjugates were produced by simple incubation and formed conjugates were analyzed for the efficiency of the plant extract to conjugate the drug. The therapeutic efficacy of the conjugated drug was evaluated using luciferase Reporter phage assay against M.tuberculosis H 37 RV. High drug entrapment
Precise tumor therapy requires technological progress in tumor imaging and therapy. Hypoxia is a key factor involved in the whole tumor genesis, growth, metastasis, and inva- siveness processes. Investigating hypoxia distribution and understanding the hypoxia condition in tumor areas can greatly contribute to cancer diagnosis and therapy. The current multifunctional hypoxia nanoparticles have numerous advantages and have achieved great progress in the detection of tumor and the guidance of tumor therapy in the laboratory. Multimodal hypoxia imaging helps rapidly locate tumor regions non-invasively and obtain functional images of tumor areas. Hypoxia imaging-guided tumor therapy can monitor the therapy process and evaluate the therapeutic efficiency. However, many challenges remain in the clinical application of this technology. The issues of signal transmission, therapeutic effect estimating standard, and the combination of multimodal hypoxia imaging need to be addressed. Overall, the multifunctional hypoxia nanopar- ticle is a promising and powerful tool for treating tumor, and multimodal optical hypoxia imaging. Hypoxia-guided tumor therapy can substantially contribute to precise tumor theranostic.
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Several lines of evidence have revealed that Bmi1 asso- ciates with malignant transformation of precancerous lesions, EMT and CSCs maintenance of HNSCC [9, 13, 24]. Elevated Bmi1 usually correlated with aggressive fea- tures and unfavorable patients’ survival [11, 13, 20, 25]. Our previous study has found that Bmi1 was aberrantly overexpressed in oral tongue cancer and it was potently inhibited by HDACi (inhibitors of histone deacetylases) chemicals, which in turn resulted in impaired tumor growth. However, these chemicals are not specific and might induced unwanted downstream effects beyond Bmi1 inhibition . In the present study, we sought to determine the therapeutic efficiency of PTC-209, a novel and selective inhibitor of Bmi1, against HNSCC using both in vitro cell culture and in vivo xenograft animal model.
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The objective of the present research work was to design, develop and optimize Letrozole loaded polymeric nanoparticles in order to potentially maximize the therapeutic efficiency, to decrease toxicity as well as to minimize the drug side effects. Pectin and Tween 80 were used as polymer and surfactants respectively. Letrozole polymeric nanoparticles (LTZ-PNPs) were prepared by precipitation method. The drug - polymer compatibility was studied using Fourier Transform Infrared (FTIR) and Differential Scanning Microscopy (DSC). The formulations’ optimization was done by design expert. The drug content (DC) and entrapment efficiency (EE) of nanoparticles (NPs) were evaluated by UV-Vis microscopy. The particle size of NPs were investigated using dynamic light scattering technique. The Franz diffusion cell was used for In-Vitro drug release studies. Accelerated stability studies were performed as per ICH guidelines. FTIR and DSC studies revealed compatibility between Letrozole and pectin. The DC was found to be uniform within all formulations (95%) and 96.87 % for the optimized formulation (F9). The E.E was found to be in the range of 68.87 to 95.11%. The NPs particle size was between 194 nm and 333 nm; F9 showed the particle size of 218.5 nm. Drug release from all formulated NPs followed non - fickian transport, thus the release mechanism was diffusion. The optimized formulation did not show a large variation in DC and EE when stored at 40 °C/75% RH as per ICH guidelines.
This current study explores Chinese primary school psychological counsellors ’ subjective experience and viewpoints on the therapeutic use of stories and storytelling. Therapeutic storytelling is defined within this article as the process of using a predesigned therapeutic story in the practice of psychological counselling with the aim of having a therapeutic effect upon the client or clients. A related approach is the co-construction of the story, where the therapeutic story is not predesigned but developed by counsellor and client as part of the therapeutic intervention. Based on the guidelines for constructing therapeutic stories developed by Sunderland (2004), the author created four therapeutic stories for the participants to use. As suggested by Sunderland (2004), the main character of the story first employs destructive coping strategies for the problems encountered, and the coping strategies resemble those often used by children in similar situations. Such coping strategies result in crisis in the main character’s life, and then other characters appear in the story and help the main character adopt Ba new behaviour, way of being or coping mechanism, and [then] feels a lot better^ (Sunderland 2004, p. 23). The stories involved were adapted from Chinese myths and historical tales and targeted common problems including examination anxiety, social with- drawal, separation/loss, and adapting to changes (such as transferring to a new school). For example, ‘ The Magical Lotus Lantern ’ , which is a Chinese mythological tale about a half-god boy rescuing his mother who was a goddess imprisoned underneath a great mountain for marrying his mortal father, was adapted to target children ’ s mental health problems related to separation and loss.
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Net mechanical efficiency of walking ( E net ) is a common physiological method used to evaluate walking and the metabolic consequences of gait deficits. This measure determines the magnitude of metabolic energy expend- iture converted into mechanical work during walking. Gait deficits such as those in Parkinson’s disease increase the metabolic cost of walking and reduce E net  . Conse- quently, patients with poor E net use excessive amounts of energy to sustain a given sub-maximal workload, which contributes to an elevated level of physical fatigue. Findings from our lab indicate that E net is reduced in
Certain molecular techniques, while yielding new informa- tion, have limitations. DNA transfer by transfection has low efficiency in easily transfectable transformed cell lines (e.g. HEK 293, COS, CHO), but almost no efficiency in normal ‘primary’ cells. Low-efficiency DNA transfection need not be a rate-limiting step, as cells stably transfected with DNA can be detected, sorted or cloned. However, there are problems that cannot be overcome. One problem is that transfectable cells from certain lineages such as macrophages, a cell type of major importance in inflammation and chronic rheumatoid diseases, are specialised to degrade exogenous material (such as DNA) and consequently do not transfect. Gene function in one cell type may not be identical to that in another; hence, conclusions made in transfectable cell lin- eages may not extrapolate to other nontransfectable cells. Furthermore, transformed cell lines have enormous abnor- malities in their genomes, with deletions, duplications and alterations in chromosome number.
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Based on the guidelines for creating therapeutic stories proposed by Sunderland (2001), I developed four therapeutic stories targeting Chinese primary school students’ common mental health problems, including examination anxiety, social withdrawal, separation/loss, and adaptation problems. Generally, therapeutic storytelling was a new technique for the participants involved in this study. Hence, I delivered an online presentation to each participant to introduce the basic concept of therapeutic storytelling and present the stories devised by me. The participants were encouraged to use the stories in their practice, and eight of the participants found the opportunity to deliver the stories. Semi-structured interviews were conducted to explore the participants’ viewpoints and experiences regarding the therapeutic use of stories and storytelling. I was aware that the online presentation might somehow influence the participants’ views of therapeutic storytelling. Therefore, during the interviews, I guided the participants to focus on their own experience and understanding and discuss this therapeutic technique critically.
Restorative Emotion Scripts. Restorative emotion scripts enable emotional release that promotes well-being. The majority of respondents live in Scotland where the social order is “undemonstrative,” requiring a “stiff upper lip.” Respondents regard their home environments as being “emotionally straightjacketed,” you “don’t show emotion,” especially not in public and, for some, not even in private. James shares that “typically, where I’m from people are very introverted and don’t like to show their emotions but Lourdes brings it out and that is really quite profound.” These comments are reminiscent of Craig’s (2004) assessment of the dominance of logic over emotion within the Scottish culture and a national character that is fearful of drawing attention to oneself. The performance of sentiments (Gopaldas 2014) is largely absent within respondents’ home towns. This is why the Lourdes therapeutic servicescape is viewed as a “profound” opportunity to release emotional suffering:
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Melarsoprol, a trivalent organic arsenical compound, has been the drug of choice for second-stage HAT caused by either T. b. gam- biense or T. b. rhodesiense since 1949. Melarsoprol is liposoluble and for this reason can cross the blood brain barrier (Nok 2003); however, being insoluble in water, it must be administered strictly intravenously after being dissolved in propylene glycol, which is highly irritating to tissues. As a result, the administration of melar- soprol is very painful (Nok 2003). The most appropriate regimen is not yet agreed upon and various regimens are currently in use. Melarsoprol causes a variety of adverse reactions, but the most se- rious is an encephalopathic syndrome. The incidence of this com- plication varies from 1.5% to 28% of all melarsoprol treatments, with a median associated fatality rate of 50% (Seixas 2005); be- cause of this risk, treatment with melarsoprol requires hospitaliza- tion of the patient (Stich 2003). High rates of therapeutic failure have been observed in the Democratic Republic of Congo, An- gola, and Sudan (Legros 2002).
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The transduction process itself is influenced by many variables. Although the same batch of vector supernatant was used, all cell transductions were performed on different days after isolation from the tissue due to the expansion procedure. The thawing of the supernatant, cell counting and cell preparation, timing, the mixing of the supernatant with the cells and the seeding are many work steps that had impact on the transduction efficiency. In addition, a SIN-gamma retroviral vector only infects dividing cells. The fact that the cell division rate, respectively population-doubling time in all batches highly varied (see Figure 11) led to additional variances. Confirming these reservations, the mean insertion rate and the transduction efficacy were highest for batch Human 4, although the population-doubling time was the slowest during the whole production. It stands to reason that the whole transduction approach is more important than the single aspect of a cell division rate. Method optimization to increase transduction efficiency is an ongoing challenge in the field of cell-based gene therapy [298-300]. This argument is supported by the fact that method B showed the highest transduction efficiency even though the MOI stayed the same. The methods were basically the same but were manipulated during the joining of viral supernatant and cells. Method A, the method with the lowest transduction efficacy (3%), was the simple dispersing of cells and virus. If the viral supernatant was centrifuged on PLL- containing plates and the cells were seeded into these wells (method B), the percentage of transduced cells multiplied (46%). This was accomplished despite using the same virus / cell ratio. These results show that the way through which virus and cells are joined affects the transduction efficiency more than the numerical virus / cell ratio.
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From a health systems perspective, a MNC should help to control the level of pharmaceutical spending within a health system by limiting the development of so-called ‘me-too drugs’ – drugs that are ‘minor variations of drugs already on the market (Angell, 2004: 21) and which consume R&D resources and diminish incentives for innovation (Hollis, 2004: 1). It can be argued that allowing me-too drugs, and therefore encouraging competition and duplication within the same therapeutic class of medicine, might increase doctor and patient choice, offer a drug more easily tolerated by certain groups of patients, or even reduce expenditure by encouraging price competition (Garattini, 1997). However, when these drugs are brought onto the market and heavily promoted as the originator drug goes ‘off patent’, the potential to increase consumption of the more expensive me-too drug is likely to outweigh potential cost benefits (Morgan et al., 2005) . By encouraging the creation of a regulatory environment where it is less profitable to develop drugs that are unlikely to be therapeutic advances, socially responsible (rather than market-oriented) research and innovation would be incentivised (Nathan, 2007: 304).
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