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??The nutritional status of patients and the constituents of their diet can significantly impact the pharmacokinetic and pharmacodynamic properties of drugs. The drugs can also interfere the digestion and absorption of various nutrients and nutrition status of patient’s through the drug’s metabolism and actions. When developing a therapeutic plan for the pediatric patient??it is important that practitioners consider the interactions that occur among nutritional status??age??disease state??and drug action.     

Interaction of nutrition and infection in clinical practice.

Resistance to infection is determined by a great many interralted factors, but one of the most significant variables is nutritional status of the host. The interaction between nutrition and infection has been described as synergistic, with malnutrition reducing resistance to infection, and infection, in turn, negatively affecting nutritional status. There are qualitative if not quantitative similarities between the evidence that has been gathered from studies of children living in vast areas of the developing countries, in which high rates of both severe malnutrition and infectious diseases are linked with high mortality rates, and evidence from studies of disadvantages children living in the United States in economically depressed migrant camps, Indian reservations, or rural and urban poverty, or children compromised by debilitating chronic diseases. Maternal nutritional status during pregnancy must receive more attention as a factor in the newborn's resistance to infection. Intrauterine malnutrition may cause impaired cellular immune function in the small-for-date infant which persists throughout the first year of life. Further research is needed to clarify this relationship. The optimal management of infections includes management or maintenance of nutritional status, and, in turn, management of nutritional deficiencies include prevention and treatment of infections.     

Interaction between methotrexate and ciprofloxacin

High-dose methotrexate is used in malignant hemopathies and solid tumors in children. Methotrexate serum concentrations must be monitored because of the possible toxicity of drug elimination delay. Several drugs (e.g., penicillin, probenecid) can alter the elimination of methotrexate. The authors report two cases of delayed elimination of methotrexate in patients receiving ciprofloxacin, with severe toxicity.     

Interaction between chloramphenicol and acetaminophen.

Acetaminophen has been reported either to prolong or not to affect the clearance of chloramphenicol. To confirm one of these findings we studied the clearance of chloramphenicol and its metabolites using high pressure liquid chromatography in five patients (ages 2.5 to 5 years) before and during oral treatment with acetaminophen (50 mg/kg/day). Significant differences were observed in mean (SD) peak serum chloramphenicol concentration (-9.7 (3.2) mg/l), mean (SD) apparent volume of distribution (+225 (162) ml/kg), mean (SD) chloramphenicol half life (-1.9 (1.1) hours), mean (SD) chloramphenicol clearance (+236 (94) ml/kg/h), mean (SD) area under the curve (-83.5 (33.0) mg/l/h), and mean (SD) elimination constant (+0.34 (0.13) h-1) between samples obtained before and during treatment with acetaminophen. Acetaminophen, when given orally for several days, increased the clearance of chloramphenicol, perhaps by increased glucuronidation. This report re-emphasises the need for therapeutic drug monitoring whenever these two drugs are used together.     

Fascinating Interaction between Host and Pathogen

Clinical manifestations of disease depend upon host’s immune response that is induced by pathogen and modified by the host’s innate and adaptive immunity. Immunocompetent children of similar age and nutrition evoke different responses to the same pathogen varying from benign to potentially fatal condition. This results in diverse clinical presentations of a disease, that is different from the standard expected pattern and thus, poses a diagnostic challenge. Even, subsequent progression of a disease is also variable. It is the balance between immune stimulation, immune suppression and immune tolerance that decides the outcome. In case of balanced response, child recovers completely without any damage. However at times, cure is at the expense of permanent sequalae while in case of unfavourable immune response, survival may not be certain inspite of successful therapy. Symptoms and physical signs of primary disease often overlap with those caused by host’s immune response. In such a situation, it is difficult to decide whether therapy of primary disease has failed due to drug resistance or whether persistence or deterioration is the result of immune response. Occasionally pathogen can transform into “superantigen” that may lead to “cytokine storm”. Resulting immune-mediated complications may endanger life and at best, treated symptomatically. Immune suppressive drugs such as steroids, chemotherapeutic agents, IVIG or specific antibodies may not be able to suppress undesirable immune response. It is not just the immune suppression that is required but ideally immune modulation. Immune modulation refers to enhancing protective responses while avoiding destructive ones. At present, science falls short of anticipating harmful immune responses and lacks specific immune intervention. Laboratory test results are also dependent on host response and hence need cautious interpretation based on clinical profile in consideration with multiple variables. In final analysis, fight between host and pathogen is a complex one and often unpredictable. It is hoped that most children evoke favourable response but pediatrician has to be watchful even in the most benign disease.     

Relationship between nutrition and development in Kenyan toddlers

The relationship between mild to moderate malnutrition, as measured by food intake and anthropometric status, and developmental outcome was explored in 110 Kenyan toddlers. Developmental outcome was assessed at 30 months of age by the Bayley Mental and Motor scales and by evaluation of play behaviors. Verbalization and play during months 15 to 30 were also evaluated. Family background and home rearing conditions were assessed, and these variables were separated from the correlations between nutrition and outcome by partial correlation methods. Food intake was related to anthropometric status, play behaviors, and total amount of verbalization and play even when the potentially confounding effects of certain family background and home rearing variables were covaried. Food intake was not related to Bayley Mental and Motor scores, but measures of length and weight were, even when family background and home rearing variables were held constant. Mild to moderate malnutrition does appear to affect the child's development adversely even when other environmental characteristics, which also relate to development, are considered.     

流感病毒与肺炎链球菌相互作用的机制

流感死亡病例多与继发细菌感染,尤其是肺炎链球菌感染有关.病毒感染损伤正常保护性上皮层,引起小气道阻塞等呼吸道功能改变,有利于细菌定植和繁殖.流感病毒感染后的免疫反应也有利于继发细菌感染.细菌可增强病毒的致病力,细菌产生的蛋白酶可以裂解活化病毒血凝素的糖蛋白,使其获得感染力.细菌感染与原发流感病毒感染同时存在的患者症状严...     

硫化氢与一氧化氮的相互作用

硫化氢(H2S)是继一氧化氮(NO)和一氧化碳之后发现的又一种新的气体信号分子,在心血管系统中发挥重要的病理生理作用。随着心血管疾病病理生理机制的不断被阐明,气体信号分子之间的相互作用是该领域普遍关注的重要问题。本文对H2S和NO的相互作用进行总结,旨在明确气体信号分子间的相互调节体系,对深入了解心血管系统疾病的病理生理变化具有重大意义。     

Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia

Because trimethoprim-sulfamethoxazole (TMP-SMX) causes neutropenia in children with leukemia, we investigated the possibility that pharmacokinetic interaction between methotrexate (MTX) and TMP-SMX causes accumulation of the antileukemia agent. We studied the pharmacokinetics of MTX given intravenously or orally to nine children with acute lymphoblastic leukemia, once with and once without TMP-SMX. There was an increase in free MTX fraction during TMP-SMX therapy in all patients, from (mean +/- SD) 37.4 +/- 11% without TMP-SMX to 52.2 +/- 6.4% with TMP-SMX (p less than 0.01). Plasma clearance of total MTX did not change significantly, whereas clearance of free MTX decreased significantly (from 12.5 +/- 4 to 7.6 +/- 1.5 ml/kg/min; p less than 0.05). There was a consistent decrease in the renal clearance of free MTX (from 12.1 +/- 6.8 to 5.6 +/- 2.4 ml/kg/min; p less than 0.05). Elimination half-life of MTX was not affected significantly by TMP-SMX. There was a significant correlation between serum concentrations of TMP-SMX and the percentage of decrease in the renal clearance of free MTX (r = 0.91; p less than 0.05). These changes in protein binding and tubular clearance of MTX, caused by competition with TMP-SMX, result in a mean 66% increase in systemic exposure to MTX and may explain the myelotoxicity often observed with the coadministration of the two drugs.