Chlorodesmethyldiazepam (I) concentrations were followed for 72 h in the plasma of four volunteers given 2 mg of the drug orally. The drug appears to be well absorbed, reaching peak plasma levels of 20--30 ng ml-1 1--2 h after administration; 72 h after administration, plasma concentrations are still measurable (5 ng ml-1). The analytical method involved a single extraction of I from the plasma into benzene followed by centrifugation, evaporation, and gas-chromatographic analysis of the samples.

Administration, Oral↗

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Content of methylhistidines in normal and pathological human skeletal muscles.

The content of 3-methylhistidine (3-MH) and 1-methylhistidine (1-MH) was measured in muscle biopsy specimens from 13 normal controls, 19 patients with Duchenne muscular dystrophy, 8 limb-girdle disease patients, and 23 disease controls with different forms of muscular pathology. 3-MH and 1-MH concentrations in normal human muscle did not appear to be influenced by sex, body weight, and age, at least for subjects in the 10--60 year age group examined. Skeletal muscle 1-MH levels did not significantly differ from mean control values in any of the pathologies investigated. In the patient population examined, the mean 3-MH level per unit of noncollagen protein (NCP) was significantly lower than normal in Duchenne dystrophy only, the reduction being related to disease severity. The significantly lower concentrations of 3-MH in muscle of Duchenne patients indicate the importance of measuring 3-MH in diseased muscle to obtain reliable estimates of the myofibrillar protein catabolic rate.

Adolescent↗

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Mycobacterium tuberculosis heat shock protein 10 increases both proliferation and death in mouse P19 teratocarcinoma cells.

Exogenously added Mycobacterium tuberculosis Hsp10, either synthetic or recombinant, but not other related heat shock proteins (GroES from Escherichia coli or bovine Ubiquitin), increases apoptosis in serum-deprived P19 mouse teratocarcinoma cells. The effect is dose-dependent, with a bell-shaped curve and peak activity at 10(-9) M (maximal effect: 62.9 +/- 17.7% increase, mean +/- SD, n = 10) and is specifically inhibited by a polyclonal antibody raised against the synthetic protein. On the other hand, when the same cells are exponentially growing, M. tuberculosis Hsp10 increases cell proliferation with a bell-shaped dose-response curve and a moderate decrease in potency (peak-activity at 10(-8)-10(-7) M, with a 43.7 +/- 8.1% increase, mean +/- SD, n = 3). Therefore, it appears that this bacterial protein can exert two opposite effects, behaving either as a death- or as a growth-promoting factor, depending on the conditions of the target.

Animals↗

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Anticonvulsant activity and brain levels of diazepam and its metabolites in mice.

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Animals↗

PubMedDate not supplied

An extensively hydrolysed cow's milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants.

BACKGROUND: About 20 % of infants fed with breast-milk substitutes suffer from Gastro Esophageal Reflux (GER) and 1/3 of them also show Cow's Milk Allergy (CMA) symptoms. METHODS: We planned this study to assess by dynamic echography the usefulness of an Extensively Hydrolysed Cow's Milk Formula (eHF) in infants suffering from GER. Ten infants showing GER symptoms and 10 normal babies, all fed with breast-milk substitutes, were enrolled. Clinical symptom scores related to GER were assessed for one week. The Gastric Emptying Time (GET) was determined by means of dynamic echography after feeding with cow's milk-derived formulae and again after a week feeding with eHF in subjects previously showing GER symptoms. RESULTS: All infants with a clinical diagnosis for GER showed an abnormally high average GET in comparison to normal subjects (205 vs 124 min, p = 0.000). Switching to the eHF led to a significant clinical improvement (p = 0.0039) especially in babies skin-test and RAST positive to cow's milk, and to a significant decrease toward the normal value of the GET (167 min, p < 0.001). CONCLUSIONS: The eHF tested improves GER symptoms in infants suffering from this disease. Our experience confirms and supports the use of dynamic echography as a reliable, simple, and non-invasive diagnostic method for infants with an increased GET associated with clinical symptoms of GER.

Animals↗

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CD34+ cells in peripheral blood of healthy human beings and allergic subjects: clue to acute and minimal persistent inflammation.

BACKGROUND: There is compelling evidence that hemopoietic precursor cells (HPC) play a crucial role in establishing cellular inflammation in allergic diseases. Increased levels of circulating CD34+ HPC committed to the myeloid lineage have been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+ cells have been identified within the cellular infiltrates of tissues, at peripheral sites of inflammation. METHOD: We conducted a pilot study to evaluate CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine women; mean age 28.9 years), independently of treatment. The patients presented rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+ cells were quantified at enrollment (T0), one year later (T1) and two years later (T2). The severity of symptoms was graded on a five-point scale (0 = absence of symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10 women; mean age 24.5 years) were evaluated as controls. To obtain information about the total amount of circulating HPC, independently of the lineage commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a modification of the Milan protocol of peripheral blood CD34+ cell estimation. The cells were analyzed using a BD FACScan or FACSCalibur and the results were expressed as the percentage of positive cells. RESULTS: CD34+ cell traffic in the control group was very low since all values were < 0.10 (median value: 0.03 %). Values in the patient group were increased in both extrinsic and intrinsic forms with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The relationship between CD34+ traffic and the severity score was highly significant (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000). CONCLUSIONS: The data reported herein suggest that the method employed is effective in assessing acute allergic inflammation, as well as minimal persistent inflammation underlying an asymptomatic clinical condition. Evaluation of CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter study currently being planned together with traditional study of circulating IgE, could be a reliable non-invasive laboratory tool for monitoring allergic inflammation.

Adolescent↗

PubMedDate not supplied

Identification by in situ hybridization of IFN-beta-producing murine macrophages obtained from high and low interferon producers.

Resident peritoneal macrophages obtained from If-1h and If-1l mice were induced in vitro with Newcastle disease virus. Then, 3, 5 and 7 h after induction, the cells were fixed and analysed for the presence of Mu IFN-beta mRNA by in situ hybridization, using a 35S-labelled Mu IFN-beta cDNA as a probe. The number of cells that were scored positive was the same in cultures derived from high responder If-1h and from low responder If-1l mice, and reached 100% of the cells present in the cultures. This result highly suggests that low responder mice have the same number of IFN-producing cells as high responders, and that the difference in production is not due to an increased number of producer cells in high responders.

Animals↗

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Do tryptase, ECP and specific IgE measurement by nasal incubation increase the specific nasal provocation test sensitivity?

The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool. Fitted to reproduce natural exposure condition to pick the responsible allergen for nasal symptoms out, it is applied when prick test and RAST responses are doubtful. SNPT results have been evaluated measuring nasal resistance (anterior rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity. This study focused on the determination of allergic response markers, triggered by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal mucosa applying a new method, based on in situ incubation, before and after sNPT. The latter was performed following a standardized method. Tryptase levels increased in 13 patients (65%), were unchanged in four patients (20%), and slightly decreased in three patients (15%). The increase recorded was significant in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen allergic patients. ECP values increased in 13 patients (65%), were unchanged in two patients (10%), and highly decreased in five patients (25%). ECP increase was not significant (p> 0.05). Specific IgE levels increased in seven patients (35%), were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE increase was significant in pollen-allergic patients (p<0.05), while it was not significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE were not detected in the control group. The data obtained showed a positive sNPT response in 12 patients (60%). Comparing our results with those derived from classical-parameter employment, we gathered an improvement of 10%. On the basis of the usual parameters, in fact, we recorded 50% positivity, while the use of mediators provided an additional 10% improvement in sNPT sensitivity: taking together the usual parameters and nasal allergic mediators values, we reached an sNPT over-all sensitivity of 85%.

Adolescent↗