Urosepsis: from the intensive care viewpoint

A recent survey conducted by the Competence Network Sepsis (SepNet) revealed that severe sepsis and/or septic shock occurs in 75000 inhabitants (110 per 100,000) and sepsis occurs in 79000 inhabitants (116 per 100,000) in Germany annually. The prevalence of urosepsis in this survey was 7%. Early diagnosis of sepsis prior to the onset of clinical deterioration is of particular interest because this would increase the possibility of early and specific treatment, which in turn is the major determining factor of mortality in septic patients. Treatment of urosepsis consists of source control, early antimicrobial therapy as well as supportive and adjunctive therapy. For supportive therapy, adequate volume loading is the most important step in the treatment of patients with urosepsis in order to restore and maintain oxygen transport and tissue oxygenation. Therefore, supportive treatment should focus on adequate volume resuscitation and appropriate use of inotropes/vasopressors. The PROWESS study is the first investigation demonstrating the decrease in mortality in patients with sepsis following administration of activated protein C (APC). Thus, administration of APC to patients with two-organ failure or an APACHE II score > or =25 within the first 24 h after the first sepsis-induced organ failure is a part of adjunctive therapy. Additionally, current data support low-dose hydrocortisone therapy in patients with vasopressor-dependent severe septic shock. Time to initiation of therapy is crucial for surviving sepsis. Implementing new medical evidence in this context into daily clinical intensive care remains a major hurdle.     

Aminoglycosides from the clinical microbiologist's viewpoint.

The author is discussing the aminoglycosides from the clinical microbiologists viewpoint. It is both an review of the literature and a personal attempt to put into perspective some of his own experience with these agents and reports in the literature. He is discussing the influence of the culture media composition of the outcome of susceptibility tests with these agents as well as the problems of bacterial resistance. Furthermore the topic of rapid and reasonably accurate serum drug level determination. Finally he gives some brief comments to the question of synergism or antagonism with other mainly penicillin type antibiotics.     

Understanding ricin from a defensive viewpoint

The toxin ricin has long been understood to have potential for criminal activity and there has been concern that it might be used as a mass-scale weapon on a military basis for at least two decades. Currently, the focus has extended to encompass terrorist activities using ricin to disrupt every day activities on a smaller scale. Whichever scenario is considered, there are features in common which need to be understood; these include the knowledge of the toxicity from ricin poisoning by the likely routes, methods for the detection of ricin in relevant materials and approaches to making an early diagnosis of ricin poisoning, in order to take therapeutic steps to mitigate the toxicity. This article will review the current situation regarding each of these stages in our collective understanding of ricin and how to defend against its use by an aggressor.     

Toxic effects arising from selenium and deferasirox interaction in the biological system

This investigation was conducted to evaluate the effect of deferasirox on selenium toxicity in male rat organs. After 50 days of selenium administration, all the rats showed toxicity symptoms. After poisoning, deferasirox was given orally to rats during 10 days. The results show that toxicity symptoms were unexpectedly increased. The new symptoms of toxicity after deferasirox administration were including loss of body hairs, yellowish discoloration of hair, weakness, brown spot on their skin, enlargement of the spleen and shrinking of sex organs. Selenium and iron concentrations were determined by GFAAS and FAAS, respectively. The results indicate the poisoned rats with selenium that received deferasirox as a drug, shown serious symptoms such as exacerbate toxicity, reduction in iron concentration, anemia and even death after a few days of deferasirox administration.     

Clinicopharmacological study of gastrointestinal drugs from the viewpoint of postmarketing development

Pharmaceutical development starts with the discovery of a new compound. Drugs become commercially available after non-clinical and clinical studies, but processes that take place after marketing are also important for pharmaceutical development. In recent years, use of the phrase "Ikuyaku" meaning postmarketing development has become more common. Sometimes, the proper usage, indications and harmful effects of a drug are discovered only after it becomes commercially available and is administered to many patients. Hence, pharmacists need to actively perform postmarketing studies to reveal the true nature of drugs. In the present clinicopharmacological study, we investigated the effects of histamine H(2) receptor antagonists (H(2)-RAs) on the plasma concentrations of gastrointestinal peptides from the viewpoint of postmarketing development. First we established an enzyme immunoassay for secretin, which is involved in gastrointestinal motility. Then we used this and existing peptide assays to investigate the above-mentioned issues. Ranitidine and nizatidine increased the plasma concentration of motilin. It is believed that the plasma concentration of Ach is elevated by ranitidine and nizatidine, which possesses an anti-AchE activity, and that the increased the plasma concentration of Ach facilitated release of motilin, elevating the plasma concentration of motilin. When compared to the placebo, lafutidine significantly increased the plasma concentration of CGRP (calcitonin gene-related peptide) and substance P. Furthermore, released CGRP stimulated CGRP1 receptors to facilitate secretion of somatostatin. Therefore, lafutidine appears to protect the gastric mucosa and regulate gastrointestinal motility. The same results were obtained with ranitidine and nizatidine. While H(2)-RAs have a common function in suppressing the secretion of gastric acid, they do not exhibit the same effects on factors related to recurrence of peptic ulcer, such as gastrointestinal motility and blood flow in the gastrointestinal mucosa. Hence, measuring the plasma concentration of gastrointestinal peptides can be used to estimate the effects of drugs on gastrointestinal motility. From the viewpoint of postmarketing development, we are in the process of establishing indicators for the proper usage of pharmaceutical drugs. Pharmacists need to closely follow and monitor adverse reactions. In order to further improve monitoring of drug therapy, it will be necessary to assess not only the blood concentrations of drugs, but also biological reactions to the drugs. Since the levels of peptides reflect the clinical efficacy of gastrointestinal drugs, measuring peptide levels appears to be useful for selecting appropriate drugs.     

从药效学观点浅析抗生素的不合理应用

随着医药科技的迅猛发展，抗生素的品种日益增多，联用抗生素治疗已非常普遍。一些新的治疗方案、新的抗生素不断推出，也就增加了不合理的用药现象。现以药效学的观点就临床上常见的、有代表性的静滴用抗生素不合理应用现象作一浅析，以利提高临床用药水平。