Absence Of Secondary Effects Research Articles

Specific Quality of Life Assessment by the NutriQoL® Questionnaire Among Patients Receiving Home Enteral Nutrition.

BackgroundHome enteral nutrition (HEN), including tube feeding and oral supplementation, can improve or worsen quality of life (QoL). The specific assessment of factors affecting QoL may identify the inherent problems associated with HEN. The aim of this study was to evaluate whether the validated NutriQoL® questionnaire is useful for assessing the QoL and the factors influencing it in patients receiving HEN.MethodsA total of 78 patients receiving HEN completed both the NutriQoL and the SF‐12 questionnaires during their routine visits to nutrition service at the hospital.ResultsNinety percent of patients receiving HEN had cancer, 58% received oral supplements, and 42% received tube feeding. At recruitment, the mean score ± SD of the NutriQoL was 66 ± 14, whereas that of the SF‐12 was 40 ± 9. A positive correlation between NutriQoL and SF‐12 scores (ρ = 0.5; P < .001) was found. Multivariate analysis showed that HEN type (oral vs tube) (odds ratio [OR], 5.6; 95% CI 2.0–15.3; P = .001) and the absence of secondary effects (OR, 3.0; 95% CI, 1.2–7.9; P = .024) were both variables explaining NutriQoL results adjusted by sex and age. The SF‐12 results did not show associations with nutrition factors. On visit 2, we observed significant improvements in NutriQoL results.ConclusionThe NutriQoL questionnaire identifies specific problems that affect the QoL of patients receiving HEN, whereas SF‐12 does not. The route of entry and the occurrence of complications influence specific QoL. NutriQoL is a useful tool to identify the factors that worsen the QoL in patients receiving HEN.

Bovine Milk Lactoferrin Selectively Kills Highly Metastatic Prostate Cancer PC-3 and Osteosarcoma MG-63 Cells In Vitro.

Prostate cancer and osteosarcoma are the second most common type of cancer affecting men and the fifth most common malignancy among adolescents, respectively. The use of non-toxic natural or natural-derived products has been one of the current strategies for cancer therapy, owing to the reduced risks of induced-chemoresistance development and the absence of secondary effects. In this perspective, lactoferrin (Lf), a natural protein derived from milk, emerges as a promising anticancer agent due to its well-recognized cytotoxicity and anti-metastatic activity. Here, we aimed to ascertain the potential activity of bovine Lf (bLf) against highly metastatic cancer cells. The bLf effect on prostate PC-3 and osteosarcoma MG-63 cell lines, both displaying plasmalemmal V-ATPase, was studied and compared with the breast cancer MDA-MB-231 and the non-tumorigenic BJ-5ta cell lines. Cell proliferation, cell death, intracellular pH, lysosomal acidification, and extracellular acidification rate were evaluated. Results show that bLf inhibits proliferation, induces apoptosis, intracellular acidification, and perturbs lysosomal acidification only in highly metastatic cancer cell lines. By contrast, BJ-5ta cells are insensitive to bLf. Overall, our results establish a common mechanism of action of bLf against highly metastatic cancer cells exhibiting plasmalemmal V-ATPase. This study opens promising perspectives for further research on the anticancer role of Lf, which ultimately will contribute to its safer and more rational application in the human therapy of these life-threatening cancers.

Climaterio y menopausia.

El autor considera que el impacto que la menopausia tiene y tendrá en el futuro de la mujer peruana obliga al médico peruano y, en especial, al ginecólogo, a obtener un conocimiento amplio sobre la fisiopatología de la mujer a esta edad, las consecuencias tempranas y tardías, los medios terapéuticos disponibles y su efectividad, de manera de poder ofrecer lo más adecuado para cada caso. En toda mujer con síndrome climatérico y menopáusico y/o con perfil de riesgo de enfermedad cardiovascular u osteoporosis, se debe considerar la administración de estrógenos. La evaluación pretratamiento incluirá una buena anamnesis y un examen clínico general, de mamas y pelvis, así como el descarte de cáncer hormono dependiente. Serán de rutina el Papanicolaou y los análisis de laboratorio básicos, que incluirán de preferencia el estudio de colesterol HDL y LDL y triglícéridos. También será de utilidad en casos específicos la mamografía, la ecografía pélvica y la densitometría ósea. Decidido el uso de estrógenos, se empleará la dosis efectiva más baja, combinada con progestágenos cíclica o permanentemente si la mujer tiene útero. El seguimiento será a los 2 y 6 meses, inicialmente, y luego en forma anual, objetivando la efectividad del estrógeno y la ausencia de efectos secundarios y de cáncer. Si bien se ha demostrado los beneficios de la terapia hormonal, es posible que la expectativa de vida sólo se elevaría en menos de un año. (Ginecol. Obstet. Perú 1994; 40: 6-25).

Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.

Medial vascular calcification (MVC) is a pathological phenomenon that causes vascular stiffening and can lead to heart failure; it is common to a variety of conditions, including aging, chronic kidney disease, diabetes, obesity, and a variety of rare genetic diseases. These conditions share the common feature of tissue-nonspecific alkaline phosphatase (TNAP) upregulation in the vasculature. To evaluate the role of TNAP in MVC, we developed a mouse model that overexpresses human TNAP in vascular smooth muscle cells in an X-linked manner. Hemizygous overexpressor male mice (Tagln-Cre(+/-) ; Hprt(ALPL) (/Y) or TNAP-OE) show extensive vascular calcification, high blood pressure, and cardiac hypertrophy, and have a median age of death of 44 days, whereas the cardiovascular phenotype is much less pronounced and life expectancy is longer in heterozygous (Tagln-Cre(+/-) ; Hprt(ALPL) (/-) ) female TNAP-OE mice. Gene expression analysis showed upregulation of osteoblast and chondrocyte markers and decreased expression of vascular smooth muscle markers in the aortas of TNAP-OE mice. Through medicinal chemistry efforts, we developed inhibitors of TNAP with drug-like pharmacokinetic characteristics. TNAP-OE mice were treated with the prototypical TNAP inhibitor SBI-425 or vehicle to evaluate the feasibility of TNAP inhibition in vivo. Treatment with this inhibitor significantly reduced aortic calcification and cardiac hypertrophy, and extended lifespan over vehicle-treated controls, in the absence of secondary effects on the skeleton. This study shows that TNAP in the vasculature contributes to the pathology of MVC and that it is a druggable target.

Modigraf Administration Through Jejunostomy in Liver Transplant Recipient: Case Report

We report our experience with a 61-year-old patient with alcoholic and hepatitis C cirrhosis who underwent liver transplantation. On the 3rd postoperative day he presented a mediastinitis secondary to esophageal perforation produced by a Linton tube. An esophagectomy with jejunostomy was performed. Tacrolimus granules for oral suspension (Modigraf) were administered through the jejunostomy. This case report highlights the use of Modigraf and the absence of secondary effects. We observed biochemical parameters during the jejunostomy period. We discuss the administration strategy applied and whether tacrolimus granules for oral suspension by jejunostomy affect the bioavailability and its side effects.

Characterization of Determinants Important for Hepatitis C Virus p7 Function in Morphogenesis by Using trans -Complementation

Hepatitis C virus (HCV) p7 is an integral membrane protein that forms ion channels in vitro and that is crucial for the efficient assembly and release of infectious virions. Due to these properties, p7 was included in the family of viroporins that comprises proteins like influenza A virus M2 and human immunodeficiency virus type 1 (HIV-1) vpu, which alter membrane permeability and facilitate the release of infectious viruses. p7 from different HCV isolates sustains virus production with variable efficiency. Moreover, p7 determinants modulate processing at the E2/p7 and the p7/NS2 signal peptidase cleavage sites, and E2/p7 cleavage is incomplete. Consequently, it was unclear if a differential ability to sustain virus production was due to variable ion channel activity or due to alternate processing at these sites. Therefore, we developed a trans-complementation assay permitting the analysis of p7 outside of the HCV polyprotein and thus independently of processing. The rescue of p7-defective HCV genomes was accomplished by providing E2, p7, and NS2, or, in some cases, by p7 alone both in a transient complementation assay as well as in stable cell lines. In contrast, neither influenza A virus M2 nor HIV-1 vpu compensated for defective p7 in HCV morphogenesis. Thus, p7 is absolutely essential for the production of infectious HCV particles. Moreover, our data indicate that p7 can operate independently of an upstream signal sequence, and that a tyrosine residue close to the conserved dibasic motif of p7 is important for optimal virus production in the context of genotype 2a viruses. The experimental system described here should be helpful to investigate further key determinants of p7 that are essential for its structure and function in the absence of secondary effects caused by altered polyprotein processing.

Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy

Duchenne muscular dystrophy is a relatively common disease that affects skeletal muscle, leading to progressive paralysis and death. There is currently no resolutive therapy. We have developed a treatment in which we combined the effects of nitric oxide with nonsteroidal antiinflammatory activity by using HCT 1026, a nitric oxide-releasing derivative of flurbiprofen. Here, we report the results of long-term (1-year) oral treatment with HCT 1026 of two murine models for limb girdle and Duchenne muscular dystrophies (alpha-sarcoglycan-null and mdx mice). In both models, HCT 1026 significantly ameliorated the morphological, biochemical, and functional phenotype in the absence of secondary effects, efficiently slowing down disease progression. HCT 1026 acted by reducing inflammation, preventing muscle damage, and preserving the number and function of satellite cells. HCT 1026 was significantly more effective than the corticosteroid prednisolone, which was analyzed in parallel. As an additional beneficial effect, HCT 1026 enhanced the therapeutic efficacy of arterially delivered donor stem cells, by increasing 4-fold their ability to migrate and reconstitute muscle fibers. The therapeutic strategy we propose is not selective for a subset of mutations; it provides ground for immediate clinical experimentation with HCT 1026 alone, which is approved for use in humans; and it sets the stage for combined therapies with donor or autologous, genetically corrected stem cells.

Transient Soil Vapor Extraction from a Pressure‐Controlled Well

AbstractNew semianalytical solutions for transient soil vapor extraction are developed for P (pressure) or P2 linearizations of the governing air flow equation. Our method treats flow rate and wellhead pressure as two distinct variables instead of customarily coupling them together. An extraction well can be either pressure or flow rate controlled with uniform applied pressure along the screen and nonuniform radial flux. The two linearizations yield different solutions for subsurface pressures; the difference increases with applied wellhead pressure. This increasing difference serves as a constraint on the magnitude of the wellhead pressure used in a test. The P equation is preferred for simulating the vadose zone pressure because it allows for more flexible implementation of boundary conditions. The solutions cover the common field test condition of unrestricted flow of atmospheric air into the vadose zone and can be readily modified for a leaky confining layer or time‐varying pressure at the ground surface. Analysis of field test data showed that the new model can closely simulate transient subsurface pressure distribution and revealed mutual dependence of porosity θ, and permeability krand kzfor the problem analyzed. The estimated kz/krwas greater than 1, higher than would be expected for natural soil in the absence of secondary effects on permeability, such as vertical cracks.

Reconsidering differential aeration cells

The differential aeration cells are responsible in practice for multiple corrosion forms. The established tension gradients between the cathodic and anodic areas are quite reduced, and consequently both electrodes stay submitted also to corrosion phenomena due to local-action cells. By analysing the theoretical current–potential curves it is shown that differential aeration cells are not responsible for an increase of the electrode corrosion in the oxygen-starved electrolyte in the absence of secondary effects. Differential aeration cells developed on normal carbon steel were investigated in H 2CO 3/HCO 3 −/CO 3 2− solutions of different pH values. The results from polarization data and immersion corrosion tests of coupling indicated have shown the following: (1) the electrode in the aerated zone, for each one of the chosen pH, tends to attain the same potential of the electrode in the deaerated zone; (2) an alkalization of the electrolyte in the aerated and deaerated zones for initial pH 5 and 7.5 in the system; (3) the current density that cross the macrocell is little, of the same order for all pH, and does not justify the observed corrosion rate in both electrodes; (4) there is a polarity inversion of the electrodes for the pH 5 and 7.5; (4) the observed corrosion rate in each one of the tested solutions was practically the same for the aerated and deaerated electrodes. An explanation for this behaviour is given.

The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110α) Pathway

Insulin-like growth factor 1 (IGF1) was considered a potential candidate for the treatment of heart failure. However, some animal studies and clinical trials have questioned whether elevating IGF1 chronically is beneficial. Secondary effects of increased serum IGF1 levels on other tissues may explain these unfavorable results. The aim of the current study was to examine the role of IGF1 in cardiac myocytes in the absence of secondary effects, and to elucidate downstream signaling pathways and transcriptional regulatory effects of the IGF1 receptor (IGF1R). Transgenic mice overexpressing IGF1R in the heart displayed cardiac hypertrophy, which was the result of an increase in myocyte size, and there was no evidence of histopathology. IGF1R transgenics also displayed enhanced systolic function at 3 months of age, and this was maintained at 12-16 months of age. The phosphoinositide 3-kinase (PI3K)-Akt-p70S6K1 pathway was significantly activated in hearts from IGF1R transgenics. Cardiac hypertrophy induced by overexpression of IGF1R was completely blocked by a dominant negative PI3K(p110alpha) mutant, suggesting IGF1R promotes compensated cardiac hypertrophy in a PI3K(p110alpha)-dependent manner. This study suggests that targeting the cardiac IGF1R-PI3K(p110alpha) pathway could be a potential therapeutic strategy for the treatment of heart failure.

A Comparative Study of Ultrasonography with Magnetic Resonance Imaging in Patients with Painful Shoulder

The recent improvement of musculoskeletal imaging achieved by high-frequency ultrasonography (US) and its important advantages as a routine dynamic imaging tool-providing results rapidly, absence of secondary effects, and low cost-make US a very useful tool in rheumatologic practice. We prospectively compared high-frequency US with magnetic resonance imaging (MRI) in patients with painful shoulder syndrome.Thirty-four consecutive patients (36 shoulders) with a first flare of shoulder pain were included in the study. US and MRI shoulder examination were performed within 2 weeks. US shoulder examinations were performed by a rheumatologist experienced in US, without knowledge of the MRI results. The MRI results were considered the gold standard. US showed high sensitivity, specificity, and positive and negative predictive values (range 85.7%-100%) in the diagnosis of tendinitis, partial-thickness, and full-thickness tear of the rotator cuff and degenerative changes of the acromio-clavicular joint. Rotator cuff calcifications were detected only by US. We highly recommend that for many painful shoulders, appropriately trained rheumatologists can perform US examinations to establish an accurate diagnosis and, thereby, improve therapy.

Further studies on the origin and nature of the bovine para-κ-casein components

1. 1.|In the absence of secondary effects, the insoluble product of rennin (EC 3.4.4.3) action on S-carboxymethyl- κ-casein (SCM-κ-casein) consists of two components, para-SCM-κ-caseins I and II. The C-terminal sequences of the separated species are identical, and this very strongly suggests that the rennin-sensitive bond in the precursor molecule (κ-casein I or II) which gives rise to each is the same. 2. 2.|By treatment with concentrated urea over extended periods of time it is possible to bring about a serial conversion of the para-SCM-κ-casein components to ones carrying a higher net negative charge. This is most probably caused by reaction of the protein species with cyanate derived from urea. Thus, it is not necessary to invoke an attack by rennin at more than one site in each κ-casein molecule to explain observations by other workers of changes in the relative amounts of para-κ-caseins I and II as well as the appearance of a third and more negatively charged species.

Naloxone in heroin dependence.

Naloxone is a potent and rapidly acting narcotic antagonist, with a duration of action which is shorter (3 to 4 hours) than that of heroin. In a clinical trial of naloxone in the treatment of heroin dependence, a daily oral dose of 100 mg. at 8 A.M. and 7 P.M. effectively blockaded 20 mg. of heroin, with partial blockade of 40 mg., for up to 10 hours after the morning dose. In narcotic antagonism therapy of opiate dependence, naloxone has the advantages of potency, rapid action, absence of secondary effects, and acceptability. It has the disadvantages of brief action and high cost.

The Short-Run Effects of Instalment Credit Control

In an earlier paper, I presented an analysis of the intermediate-run effects of instalment credit control, that is, the effects prevailing after the new credit terms have fully replaced the old ones. Although brief reference was made there to the effects of control in the short run, that is, in the time periods immediately following the change in credit terms, yet several interesting questions regarding the short run had to be ignored because of the scope of that paper. One may ask, for example: Does the down-payment effect tend to grow or diminish in strength from one period to the next during the transition from old credit terms to new ones? What about the maturity effect? Do these effects change with time, if at all, at a steady rate? In one direction only, or with reversals)? And how will different types of consumer reaction to new credit terms, as reflected in the amount of credit purchases, modify the down-payment and maturity effects, especially when there is perversity? These questions are important because for purposes of credit control policy, the short-run effects are in many cases more relevant than the intermediate-run effects. The present paper seeks to answer these questions.As the questions themselves suggest, the following discussion will be principally concerned with the delineation of the time paths of effects of credit term changes. In this sense, then, the paper pertains to the realm of “dynamics,” in contrast to the comparative-statics orientation of the earlier article. As in the earlier paper, I shall assume (a) a constant rate of growth of credit purchases before control, (b) uniform down-payment and maturity terms on all credit purchases, (c) straight-line amortization of all instalment debts, and (d) the absence of secondary effects. But instead of assuming that new credit terms will always result in a new (fixed) rate of growth of instalment purchases, I shall also consider several other types of consumer reaction. Finally, to make the analysis more general, the concept “marginal propensity to cut outlays for down payments” will be introduced, to supplement the “marginal propensity to cut outlays for instalments” used in the other paper.