Kriterien für die Zulassung von Tierarzneimitteln gegen Zeckenbefall bei Hunden und Katzen: Ein Überblick der aktuellen Anforderungen und Möglichkeiten unter Berücksichtigung der derzeitig gültigen Leitlinien

Ohne Zusammenfassung The online version of the original article can be found under doi:.     

Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices--final report of a placebo-controlled, double-blind study

One hundred and six episodes of bleeding from esophageal or gastric varices in 72 patients with cirrhosis of the liver were randomized to treatment either with intravenous terlipressin 2 mg initially and 1 mg every four hours for 24 hours together with bolus injection and continuous infusion of placebo, or with somatostatin 250 micrograms as a bolus and continuous infusion of 250 micrograms/h somatostatin for 24 hours and placebo injections. Standard treatment with transfusions, fluid and electrolyte correction, and lactulose was administered in both groups. In the terlipressin group, 48 out of 53 bleeding episodes (91%) and in the somatostatin group 43 out of 53 bleeds (81%) were initially stopped by the vasoactive drugs. Four of the five bleeds not arrested by terlipressin, and nine of the ten bleeds not arrested by somatostatin, were stopped by balloon tamponade. In one patient in each group variceal bleeding could not be stopped initially, and both patients died. The failure rate of the vasoactive treatment alone, including rebleeds within the study period, was 17% in the terlipressin, and 28% in the somatostatin, group. The initial hemostasis, including balloon tamponade, were 98%, and the definitive bleeding control rates were 89% in both groups. The hospital mortality rate was 21% (11/53) in the terlipressin, and 21% (11/53) in the somatostatin, group. Blood transfusions and duration of bleeding did not differ significantly. The study indicates that a large proportion of bleeds from esophageal and fundic varices can be stopped initially (86%) and definitively controlled (77%) by vasoactive drugs alone.     

停止强制驱逐——来自巴西库里蒂巴的报告

2003年10月1日清晨，城市警卫队的队员在巴西的库里蒂巴对一处叫Sambaqui的贫民窟住区进行了封锁，把居住在那里的72个人从他们的家中驱赶了出去。警卫队摧毁了这些人的房屋，点燃大火，把屋子里的床垫、器具和其它的日用品，甚至还包括一名老妇人喂养的小猫都丢进了大火中。武装的警卫队员还在一次未经官方批准的行动中对六个人实施了殴打。那些从自己的家园被驱赶出来的人不得不暂时住在为他们提供的一处市中心的工会大楼中。     

Augmented platelet aggregation as predictor of reocclusion after thrombolysis in acute myocardial infarction

RATIONALE: Reocclusion after thrombolysis diminishes the benefits of early reperfusion after acute myocardial infarction (AMI). No clinical or laboratory variables have been identified as predictors for reocclusion yet. METHODS AND RESULTS: To evaluate hemostatic variables as potential risk determinants platelet aggregation (PA, representing platelet activity), thrombin/antithrombin complexes (TAT, representing thrombin generation), and plasminogen activator inhibitor type 1 (PAI-1, representing endogenous fibrinolysis) were determined in 31 patients with AMI at 0, 1, 2. and 12 h after the start of thrombolysis as well as at hospital discharge. Reocclusion (defined as reinfarction or angiographically confirmed, clinically silent coronary reocclusion) occurred in 5 patients within 5-14 days and in 8 patients within 1 year. TAT plasma concentrations were lower in patients with reocclusion than in those without (9.9+/-5.7 vs. 22.9+/-22.2 ng/ml at 2 h, 6.5+/-3.1 vs. 1 1.2+/-6.4 ng/ml at 12 h, means+/-SD, p <0.05 each). Neither concentration nor activity of PAI-1 in plasma differed between both patient groups. However, both slope and maximum of PA (induced by 2 micromol/l ADP) were augmented in patients with reocclusion (slope: 39.4+/-1.7 vs. 32.5+/-7.4 at 2 h, p <0.001; 42.6+/-2.6 vs. 36.6+/-8.9 at 12 h, p <0.01). Results were independent of the thrombolytic agent used (alteplase or reteplase). A PA slope at 2 h higher than the average slope before thrombolysis (37.2+/-5.7) could be identified as best predictor for early (within 5-14 d, p=0.017, sensitivity 1.00, specificity 0.69) and late reocclusion (within 1 y, p=0.009, 0.88 and 0.74, respectively). CONCLUSIONS: Increased PA following coronary thrombolysis appears to be associated with early and late reocclusion. This marker could be useful in identifying patients who may benefit from more aggressive antiplatelet (such as GP IIb/IIIa receptor antagonists), interventional, or both strategies.     

Drying of persimmons (Diospyros kaki L.) and the following changes in the studied bioactive compounds and the total radical scavenging activities

Fresh persimmons were subjected to two different processes: sun-drying during 1 month and dehydration at 60 °C during 12 h. To assess the effect of this process on nutritional and health-related properties of persimmons dietary fibers, minerals, trace elements, polyphenols and the total radical scavenging activities (TRSAs) were determined before and after processing. It was found that the contents of dietary fibers, minerals and trace elements in fresh and dried persimmons fruits were comparable. Total polyphenols in fresh persimmons was higher than in dried fruits (1.3 vs. 0.9 and 0.8 mg/100 g FW, respectively) and percentage of inhibition was higher than in dried fruits (70% vs. 59% and 55% and 58% vs. 53% and 46% for 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) [ABTS] radicals, respectively (P>0.05 in all cases). In conclusion: (1) the differences in the contents of dietary fibers, minerals and trace elements in fresh and dried persimmons are not significant; (2) the contents of polyphenols and the level of the TRSA are higher in fresh persimmons than in dried fruits; however, both variables are also high in dried persimmons; (3) when fresh fruits are not available, proper dried persimmons could be used as a valuable substitute.     

A “Golden Age” for the discovery of new antileishmanial agents: Current status of leishmanicidal gold complexes and prospective targets beyond the trypanothione system

Leishmaniasis is one of the most neglected diseases worldwide and is considered a serious public health issue. The current therapeutic options have several disadvantages that make the search for new therapeutics urgent. Gold compounds are emerging as promising candidates based on encouraging in vitro and limited in vivo results for several Au^I and Au^III complexes. The antiparasitic mechanisms of these molecules remain only partially understood. However, a few studies have proposed the trypanothione redox system as a target, similar to the mammalian thioredoxin system, pointed out as the main target for several gold compounds with significant antitumor activity. In this review, we present the current status of the investigation and design of gold compounds directed at treating leishmaniasis. In addition, we explore potential targets in Leishmania parasites beyond the trypanothione system, taking into account previous studies and structure modulation performed for gold-based compounds.     

Stereoselective Synthesis and Antiallodynic Activity of 3-Hydroxylated Paroxetines

The design, stereoselective synthesis and in vivo antiallodynic activity of four novel paroxetine analogs, named 3-hydroxy paroxetines (3HPXs), is reported herein. Among the novel synthesized compounds, three showed an antiallodynic effect, while (R,R)-3HPX was found to be 2.5 times more bioactive than (-)-paroxetine itself in neuropathic rats. Consequently, the current investigation not only discloses a novel promising analgesic drug, but also reveals that functionalization at the C3 position of paroxetine could be as effective as the common functionalization at either C4 or within the sesamol group.     

Biosynthesis and identification of volatiles released by the myxobacterium Stigmatella aurantiaca

The volatiles released by agar plate cultures of two strains of the myxobacterium Stigmatella aurantiaca (strains Sg a15 and DW4/3-1) were collected in a closed-loop stripping apparatus (CLSA) and analyzed by GC-MS. Large numbers of substances from different compound classes (ketones, esters, lactones, terpenes, and sulfur and nitrogen compounds) were identified; several of them are reported from natural sources for the first time. The volatiles 2-methyltridecan-4-one (17), its isomer 3-methyltridecan-4-one (20), and the higher homologue 2-methyltetradecan-4-one (18) were identified in the extracts of both strains and were synthesized. In addition, strain Sg a15 produced 2,12-dimethyltridecan-4-one (19), 2-methyltridec-2-en-4-one (23), and a series of phenyl ketones, among them 1-phenyldecan-1-one (14) and 9-methyl-1-phenyldecan-1-one (16), whereas strain DW4/3-1 emitted traces of 10-methylundecan-2-one (21). The biosynthesis of 14 and 16 was examined in feeding experiments with deuterated precursors carried out on agar plate cultures. The leucine-derived starter unit isovalerate was shown to be incorporated into 16, as was phenylalanine-derived benzoic acid into both 14 and 16. The results point to formation both of the phenyl ketones and of the structurally related aliphatic ketones through an unusual head-to-head coupling between a starter unit such as benzoyl-CoA and a fatty acyl-CoA, followed by decarboxylation.     

Gas formation and biological effects of biodegradable magnesium in a preclinical and clinical observation

Magnesium alloys are biodegradable metals receiving increasing attention, but the clinical applications of these materials are delayed by concerns over the rapid corrosion rate and gas formation. Unlike corrosion, which weakens mechanical properties, the gas formation issue has received little attention. Therefore, we evaluated the gas formation and biological effects for Mg implants through preclinical (immersed in Earle’s balanced salt solution and in vivo) and clinical studies. The immersion test examined the gas volume and composition. The in vivo study also examined gas volume and histological analysis. The clinical study examined the gas volume and safety after Mg screw metatarsal fixation. Gas was mainly composed of H₂, CO and CO₂. Maximum volumes of gas formed after 5 days for in vivo and 7 days in clinical study. Within the clinical examination, two superficial wound complications healed with local wound care. Osteolytic lesions in the surrounding metaphysis of the Mg screw insertion developed in all cases and union occurred at 3 months. Mg implants released gas with variable volumes and composition (H₂, CO, and CO₂), with no long-term toxic effects on the surrounding tissue. The implants enabled bone healing, although complications of wound breakdown and osteolytic lesions developed.