The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid‐1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)‐induced lung injury in mice. For this, adult mice pre‐treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS‐challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre‐treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre‐treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI.     

Diazepam impairs place learning in naive but not in maze-experienced rats in the Morris water maze

Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.     

Influence of glycine on morphine-induced antinociception in mice

The effects of glycine on morphine-induced antinociception were investigated in mice, using a cutaneous thermal test (hot-plate), a visceral chemical test (acetylcholine writhing test), and a locomotor activity test. When glycine (200 mg/kg p.o.) and morphine (5 mg/kg s.c.) were given together during the first 30 min, glycine first antagonized the morphine-induced antinociception then this was followed by a synergistic effect. The two-phase influence of glycine on morphine-induced antinociception may be due to the interaction of glycine with different receptors.     

Typhoid fever in the neapolitan area: A case-control study

Typhoid fever is endemic in the Neapolitan area, where its yearly incidence rate largely exceeds the corresponding national figure. During the period from January to June, 1990, a matched case-control study was carried out in order to identify risk factors of the disease in this area; 51 subjects (mean age 27.2 years) with typhoid fever were compared with 102 controls matched with respect to age, sex and educational level. Consumption of raw shellfish was reported by 76.5% of the cases, as opposed to 19.6% of the controls (P < 0.01). Subjects who had eaten this food item had a 13.3-fold risk (C.I. 95% = 5.5 - 32.8) of contracting typhoid fever. In contrast, no risk was found to be associated with consumption of cooked shellfish, raw vegetables, ice-cream, non-potable water, or unpasteurized milk.The risk factor identified in this study shows that hazardous dietary habits and inadequate sewage treatment facilities, combined with lack of sanitation in the harvesting and marketing of shellfish, play a major role in the endemicity of typhoid fever in the Neapolitan area.Corresponding author.     

Comparative studies on cytotoxic and genotoxic effects of two organic mercury compounds in lymphocytes and gastric mucosa cells of sprague-dawley rats

Human lymphocytes (HL) as well as lymphocytes (RL), hepatocytes (RH), and gastric mucosa cells (GM) of Sprague-Dawley rats were treated in vitro for 1 h with methylmercury chloride (MMC, 0.5–4 μg/ml) and dimethylmercury (DMM, 5–40 μg/ml). The cytotoxicity of the two organic mercury compounds was assessed by dye exclusion, and the extent of induced DNA fragmentation was measured with a single-cell microgel electrophoresis assay. Both MMC and DMM induced DNA damage and cytotoxicity in a dose-related manner in HL, RL, and GM. MMC was more effective in causing a significant increase in median DNA migration than DMM at doses yielding approximately the same degree of cytotoxicity. In rat hepatocytes the MMC-induced DNA damage was, however, lower than in the other cells. An analysis of repair kinetics following exposure to 2 μg/ml MMC was carried out in human lymphocytes obtained from an adult male donor. The bulk of DNA repair occurred 90 min after in vitro exposure, and it was about complete by 120 min following cessation of exposure. Finally, in order to have a basis for extrapolating to the human situation, in vivo studies were performed with Sprague-Dawley rats, also assessing the DNA damage and cytotoxicity in the lymphocytes and gastric mucosa cells. These in vivo results after oral exposure may be directly compared to the in vitro data obtained in the same cells. © 1993 Wiley-Liss, Inc.     

Efficacy and safety of ciprofloxacin in the treatment of UTIs and RTIs in patients affected by liver diseases

The clinical efficacy and the safety of ciprofloxacin was studied in 92 patients (aged 26 to 83 years; mean 57.5 years) affected by urinary tract infections (UTI) and respiratory tract infections (RTI) suffering also with various liver diseases. Ciprofloxacin was given orally at different dose regimens: 500 mg b.i.d. (22 cases), 250 mg b.i.d. (20 cases), 500 mg s.i.d. (20 cases) for the treatment of UTIs; 500 mg b.i.d. (ten cases) and 250 mg b.i.d. (20 cases) for the treatment of RTIs. The doses were not correlated to the severity of the infections. Patients were treated for five to 15 days. All the bacteria isolated from sputum or urine before treatment were sensitive to ciprofloxacin (MIC range 0.015 mg/1 to 8 mg/1). The clinical and bacteriological responses were favourable in a high percentage of patients both for RTIs and UTIs, irrespective of the dose. Side effects were infrequent (7%) and mild (nausea, gastralgia, oral candidosis), never requiring the interruption of the treatment. No change in the blood chemistry tests was observed at any dose.Die klinische Wirksamkeit und Sicherheit von Ciprofloxacin wurde bei 92 Patienten (Alter 26 bis 83 Jahre, im Mittel 57,5 Jahre), die an verschiedenen Leberkrankheiten litten, bei interkurrent aufgetretenen Harnwegs- und Atemwegsinfektionen geprüft. Ciprofloxacin wurde in verschiedenen Dosierungen oral verabreicht. Zur Behandlung von Harnwegsinfektionen wurden Dosierungen von 500 mg zweimal täglich (22 Fälle), 250 mg zweimal täglich (20 Fälle) oder 500 mg in einer täglichen Einzeldosis (20 Fälle) verabreicht. Atemwegsinfektionen wurden mit zweimal täglich 500 mg (10 Fälle) oder mit zweimal täglich 250 mg (20 Fälle) behandelt. Die Dosen wurden nicht nach dem Schweregrad der Erkrankung gewählt. Die Behandlungsdauer betrug fünf bis 15 Tage. Alle aus Sputum oder Urin vor der Therapie isolierten Bakterien waren für Ciprofloxacin empfindlich (MHK-Werte 0,015 mg/l bis 8 mg/l). Bei einem hohen Prozentsatz der Patienten mit Atemwegs- und Harnwegsinfektionen wurden unabhängig von der Dosierung günstige klinische und bakteriologische Ergebnisse erzielt. Nebenwirkungen traten selten auf (7%) und waren leicht (Übelkeit, Magenschmerzen, orale Candidiasis). Ein Therapieabbruch war in keinem Fall nötig. Bei keiner der angewandten Dosierungen waren Änderungen in den klinisch-chemischen Parametern festzustellen.     

Combined skin prick and patch testing enhances identification of peanut-allergic patients with atopic dermatitis

BACKGROUND: Food atopy patch tests (APTs) are considered a useful tool for the diagnosis of food allergy. Hypersensitivity to peanuts has not been investigated by means of APTs so far. METHODS: APTs and skin prick tests (SPTs) with peanuts were performed in 136 atopic dermatitis (AD) patients. Relevance of positive and negative responses to these tests was assessed by repeated open challenges with peanuts. RESULTS: Nine percent of our AD patients reacted to the challenge. Positive responses to APTs were recorded in 19% of the patients, whereas in 12% positive SPTs were observed. APTs were more frequently positive in subjects with eczematous responses after challenge with respect to those with urticarial reactions. SPT reactivity proved to be higher in patients above 12 years of age, whereas APT positivity was more frequent in children under 6 years. APT sensitivity proved significantly higher than SPT sensitivity, in particular in children under 12 years of age. On the contrary, SPT specificity and positive predictive value were significantly higher with respect to those of APT in the age group of subjects under 6 years of age. CONCLUSIONS: Our data suggest that APTs with peanuts may represent a useful integration to standard testing modalities employed for the diagnosis of peanut allergy in AD patients.