Effect Of Double Dose Research Articles

HLA-F transcriptional and protein differential expression according to its genetic polymorphisms.

Many specificities single out HLA-F: its structure, expression regulation at cell membrane and function. HLA-F mRNA is detected in the most cell types and the protein is localized in the ER and Golgi apparatus. When expressed at cell surface, HLA-F may be associated to β2-microglobulin and peptide or expressed as an open-conformer molecule. HLA-F reaches the membrane upon activation of different primary cell types and cell-lines. HLA-F has its highest affinity for the KIR3DS1-activating NK receptor, but also binds inhibitory immune receptors. Some studies reported that HLA-F expression is associated with its genotype. Higher HLA-F mRNA expression associated with F*01:01:02, and 3 noncoding SNPs, rs1362126, rs2523405, and rs2523393, located in HLA-F-AS1 or upstream the HLA-F sequence were associated with HLA-F mRNA expression. Given the implication of HLA-F in many clinical setting, and the undisclosed process of its expression regulation, we aim to confirm the effect of the aforementioned SNPs with HLA-F transcriptional and protein expression. We analyzed the distribution, frequency and linkage disequilibrium of these SNPs at worldwide scale in the 1000 Genomes Project samples. Influence on the genotype of each SNP on HLA-F expression was explored using RNAseq data from the 1000 Genomes Project, and using Q-PCR and intracellular cytometry in PBMC from healthy individuals. Our results show that the SNPs under studied displayed remarkably different allelic proportion according to geography and confirm that rs1362126, rs2523405, and rs2523393 displayed the most concordant results, with the highest effect size and a double-dose effect.

The standard dose versus double dose of N-acetylcysteine to prevent contrast-induced nephropathy; a randomized controlled clinical trial

Background: Contrast-induced acute kidney injury (CI-AKI) is one of the possible complications in angiography, which its prevention is important. N-acetylcysteine is one of the compounds that has recently been more investigated regarding its effect on CI-AKI. Objectives: The aim of this study was to investigate the effect of standard dose and twice-thestandard of N-acetyl cysteine on prevention of contrast-induced nephropathy. Patients and Methods: In a clinical trial, 154 individuals who were referred for angiography and had glomerular filtration rate (GFR) ≤60 mL/min, enrolled in and randomly divided into two groups. Group A received the usual dose of N-acetyl cysteine and group B received twice the standard. Blood urea nitrogen (BUN), creatinine, and GFR values were measured and recorded at intervals before, 24, 48 and 72 hours after angiography. Other required laboratory parameters were also measured and recorded. Results: The results of this study indicated that the effect of double dose in males and females is not different. It also has a reverse effect on renal function in older patients. Its effect did not differ in diabetic patients compared to non-diabetic patients. N-acetyl cysteine in dose of twice the standard has not any effect on renal function in patients with hyperlipidemia, hypertension, myocardial infarction, pulmonary edema as well as smoker patients. In patients with congestive heart failure (CHF), N-acetyl cysteine in dose of twice the standard had a positive effect on renal function compared with those who did not have CHF. An interesting point in our study was the negative effect of N-acetyl cysteine in dose of twice-the-standard on renal function in patients with lower hemoglobin and hematocrit levels. Conclusions: Our study showed that an increase in the dose of N-acetyl cysteine is not effective in preventing contrast-induced nephropathy and improving renal function. Of course, in some groups, such as those with CHF, a positive effect was detected. Additionally, in some groups including patients with lower hematocrit and hemoglobin, an increase in dose is associated with a negative effect on renal function.

Genetic thromobophilia in pregnancy: a case–control study among North Indian women

In the present study, an attempt is made to understand the role of genetic thrombophilias i.e. MTHFR C677T and FVL in the causation of various pregnancy complications like pregnancy induced hypertension (PIH), recurrent abortions, intra-uterine growth retardation (IUGR) and intra-uterine death on the whole and also individually along with the comparative assessment of pathophysiological basis of various pregnancy complications via the genetic proximities. One thousand and eleven (1,011) women of reproductive age group were recruited in the present study comprising various complications and controls. Recruitment criteria for all the pregnancy complications and controls was made and followed strictly. MTHFR C677T and FVL mutation detection was done in all the subjects. Vegetarianism was found to be significant risk factors for all the pregnancy complications and also when assessed individually. With respect to MTHFR C677T polymorphism, higher frequency of 677T allele was found among controls as compared to cases. 677T allele was found to pose decreased risk for various pregnancy complications on the whole and also individually. On adjusting the diet, regression analysis revealed no risk of mutant allele (T) for various pregnancy complications. FVL homozygous mutants were found to be absent among controls. In conclusion, the present study depicts dietary pattern as one of the most important factors in demonstrating the role of MTHFR C677T in various pregnancy complications and is indicative of a relatively deleterious effect of double dose of FVL in the presently studied population. Additionally, these polymorphisms play an important role in the orchestration of PIH to IUGR and vice versa.

蕁麻疹・湿疹皮膚炎群(湿疹・皮膚炎・皮膚そう痒症・アトピー性皮膚炎)に伴うそう痒患者における塩酸フェキソフェナジンの効果と安全性(眠気)についての検討

難治性のそう痒を伴う蕁麻疹・湿疹皮膚炎群 (湿疹・皮膚炎・皮膚そう痒症・アトピー性皮膚炎) 患者に塩酸フェキソフェナジンを倍量投与し，患者のかゆみ症状と眠気の推移を visual analogue scale(VAS) の変動に関して調査を行った。そう痒を伴う蕁麻疹・皮膚炎群患者47例に対し，新規症例では塩酸フェキソフェナジン120mg投薬1～2週間にてかゆみ VAS スコアの改善が30％未満の患者に対し倍量投与を施行した。また他の抗アレルギー剤を内服中も効果不十分であると判断された切り替え症例に関しては初回から倍量投与を施行し，かゆみと眠気を VAS スコアにて評価した。新規症例では66％が120mg/日投与でかゆみ VAS30％以上改善を達成したが，達成しなかった13例のうち倍量投与によりかゆみ VAS スコアが50％以上改善した患者は8例(62％)であった。また切り替え症例9例においては全例でかゆみ VAS スコアの50％以上の改善がみられた。倍量投与に伴う日中の眠気については倍量投与群において1例のみ認められた。以上より難治性のそう痒を伴う蕁麻疹・湿疹皮膚炎群において塩酸フェキソフェナジンの倍量投与は，眠気などの副作用が少なく，かゆみの VAS スコアを低下させ得る有効な治療であると考えた。

Functional categorization of HLA-DRB1 alleles in rheumatoid arthritis: the protective effect

Because of past recombination event, human leukocyte antigen (HLA) alleles that are not closely related in overall sequence may come to resemble each other in areas coding for peptide binding regions (PBR) of HLA molecules. Peptide binding is likely to be important for the role of HLA molecules in autoimmune disease. As a result, it has been suggested that a strategy of searching for HLA disease associations that groups alleles in functional categories based on PBR motifs may be more successful than conventional strategies based on studying different alleles. Using such functional categorization, we examined the possibility of discriminating subcategories of HLA-DRB1 alleles associated with rheumatoid arthritis (RA) in a Southern French population. HLA-DRB1 genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide hybridization or sequence-specific primers. HLA-DRB1 alleles were classified according to a functional categorization that defined seven similar subregion structures or restrictive supertype patterns (RSPs) within pocket 4 of HLA-DR peptide binding groove as the molecular basis for grouping these alleles. HLA-DRB1* RSPs “A,” “De,” “Q,” “Dr,” “E,” “ R,” and “a” association with susceptibility or resistance to disease was then studied in 200 RA patients versus 200 controls. DRB1* RSP “A” containing the shared epitope alleles (DRB1*0101, *0102, *0401, *0404, *0405, *0408, *1001, *1402; odds ratio [OR] = 4.35; p c < 0.001) had a predisposing effect, with double-dose effect as expected, OR 6.68 ( p c < 0.001). Among the six remaining RSPs, two had significantly protective effect: DRB1* RSP “De” (DRB1*0103, *0402, *1102, *1103, *1301, *1302, *1304; OR = 0.33; p c < 0.001), and DRB1* RSP “Q” (DRB1*0701; OR = 0.40; p c < 0.001). One had non-significantly protective effect: DRB1* RSP “Dr” (DRB1*08, *1101, *1104, *1106, *12, *1303, *16; OR = 0.68; p < 0.05, p c = not significant [NS]). Three had neutral effect: HLA-DRB1* RSPs “E” (DRB1*0403, *0407, *0901, *1401; OR = 0.71; p = NS), “ R” (DRB1*0301, *0302; OR = 0.76; p = NS), and “a” (DRB1*1501, *1502; OR = 0.94; p = NS). The functional categorization allowed us to discriminate among the HLA-DRB1 alleles those that confer a predisposing effect, a neutral effect, and a protective effect in RA.

Preventing medication errors in the home.

Medication errors are a major problem in all settings of health care, including the home environment. The National Coordinating Council for Medication Error Reporting and Prevention (NCC-MERP) defines a medication error as any preventable event that may cause or lead to inappropriate medication use or patient harm, while the medication is in the control of the health care professional, patient, or consumer. Such events may be related to professional practice, health care products, procedures, and systems, including prescribing; order communication; product labeling, packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use. 1 This definition is important for the nurse working in the home health environment because it contains elements inherent in the nurse’s role. According to Cowley, 2 the most frequent type of medication error in the home is improper dosing. Other types of medication errors the nurse will see include documentation or transcription errors, polypharmacy, medication miscalculation, and deficient practitioner and patient knowledge. This article will address the steps the home health nurse can take to ensure the patient receives medications safely and effectively and errors are avoided. ACCURATE DOCUMENTATION Accountable and concise nursing care delivery calls for each nurse to examine the patient’s record, particularly the physician order sheet and medication record, before going into the home. This review is done whether the nurse has to administer medication or assess whether the patient or family is administering medications correctly. The patient’s medical record must be complete and the medication list updated as needed. The patient and family often are asked to document medications the former receives. For example, if the patient has a diagnosis of congestive heart failure but has gained weight since the last in-home nurse visit, the nurse can check the medication record and question the patient or family about compliance with diuretic and cardiac glycoside therapy. If the nurse has reason to question their responses, he or she should contact the physician to order possible laboratory work that will indicate the patient’s serum drug levels and help determine if the patient is receiving or taking medication as ordered. It is important for the nurse to document medication compliance or a lack thereof in the nurse’s notes. Documenting in the medical record all over-thecounter medications or herbal (nutritional) supplements the patient may be taking is also important because serious drug interactions can occur. An herbal supplement may have some of the same properties as a prescribed medication that in actuality can cause a double dose effect or have an antagonistic effect toward the prescribed medication. It becomes terribly important that the nurse knows not only the effects of prescribed medications but also those of any supplements. The nurse can use accurate medication documentation both in the patient’s medical record and the list maintained in the home to ensure the patient receives the correct medication.

Television and Violent Criminal Behavior: Beyond the Bobo Doll

This study builds on the research concerning television viewing and aggression by extending the external validity, or generalizability, of the dependent variable. We assess the relationship between self-reported television viewing at 8, 10, and 12 years of age and the subsequent commission of a violent criminal act. This study is based on interview data from 48 males incarcerated for violent crimes and 45 nonincarcerated, nonviolent males matched on age, race, and neighborhood of residence during adolescence. Results show that the extent of a respondent's reported television viewing was not, in and of itself, predictive of violent criminal acts. Instead, it was the interaction of heavy doses of television viewing and exposure to either maternal or paternal abuse that related to violent crime. These findings support the efforts of some recent scholars in their attempts to understand why television has a negative effect on only some viewers. The results are discussed in light of the cognitive formulations of neoassociationism, encoding specificity, and the double-dose effect.