Clinical and pharmacokinetic study of nimesulide in children.

The pharmacokinetic profile and efficacy of nimesulide were assessed in 2 separate studies that recruited children with hypoglycaemia or upper respiratory tract infection and fever, respectively. A single dose of nimesulide 50mg (granules) administered orally to 14 hypoglycaemic children was rapidly absorbed. A mean maximum nimesulide plasma concentration of 3.5 mg/L was achieved within 2 hours of administration, which subsequently declined over the following 12 hours. Nimesulide was metabolised to its principal hydroxy metabolite, which was detectable in samples obtained 0.5 hours after giving the parent drug. Levels of this metabolite steadily increased, surpassing those of intact nimesulide at the 9-hour sampling point. In a randomised nonblind clinical investigation, 100 hospitalised children with acute upper respiratory infections and fever received nimesulide oral suspension (5 mg/kg/day) or paracetamol (26 mg/kg/day) for 3 to 9 days. The antipyretic and anti-inflammatory effects of nimesulide were superior to those observed with paracetamol (p < 0.01) and both drugs were equally well tolerated.

Infected urachal cysts.

Infected urachal cysts present with protean clinical manifestations. Diagnosis is frequently difficult in spite of the use of modern genitourinary radiologic imaging techniques. Patients with intra-abdominal or pelvic symptoms are frequently misdiagnosed. Surgical excision is the treatment of choice for infected urachal cysts.

[The inhalational therapy of respiratory pathology]. / La terapia inalatoria nella patologia respiratoria.

The inhalation of aerosolized drugs for therapeutic purpose has been used for many years in respiratory diseases as asthma, chronic bronchitis, cystic fibrosis. Therapeutic aerosols have the advantages to deliver active substances directly to the site of disease, without systemic side effects, to produce a more rapid clinical response, to avoid barriers to the absorption of drugs such as the gastrointestinal tract. We review the mechanisms and the site of lung deposition and the range of devices that can provide an effective aerosol such as metered dose-inhaler and spacers. Besides drugs as cromolyn, beta-2-agonists and topical steroids, recently new inhalation therapies were proposed using antiviral drugs (interferon), pentamidine for Pneumocystis carinii in immunocompromised host, inhalation of attenuated virus (measles) for active immunization. However there is a need for further work in this area.

Hepatocyte adhesion to immobilized carbohydrates. I. Sugar recognition is followed by energy-dependent strengthening.

Cell-cell recognition and adhesion are thought to be complex, multistep phenomena, and may involve cell surface carbohydrates and their receptors on apposing cell surfaces. We have modeled such interactions using hepatocytes and polymer (gel) surfaces derivatized with carbohydrate ligands, and have demonstrated carbohydrate-specific cell adhesion (Schnaar, R. L., Weigel, P. H., Kuhlenschmidt, M. S., Lee, Y. C., and Roseman, S. (1978) J. Biol. Chem. 253, 7940-7951). In the present studies, we have developed a method to quantitate the forces involved in cell-gel adhesion. Our method is based on that of McClay et al. (McClay, D. R., Wessel, G. M., and Marchase, R. B. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4975-4979) which was designed to measure the forces involved in intercellular adhesion. The following results were obtained. 1) Chicken and rat hepatocytes adhere specifically to gels derivatized with N-acetylglucosamine and galactose, respectively, at either 4 degrees C or 37 degrees C. 2) At 37 degrees C, after a lag of 10-20 min, stabilization of the adhesion occurs, resulting in a 15-fold (or greater) increase in the force of adhesion. 3) This marked strengthening of adhesion does not occur at 4 degrees C and is blocked by inhibitors of oxidative phosphorylation. These data demonstrate that cells can recognize and adhere to specific carbohydrates on apposing surfaces, and can then respond by mobilizing cellular energy to strengthen that adhesion. This series of events is strikingly similar to that shown for cell-cell adhesion between hepatocytes or between neural retina cells (Umbreit, J., and Roseman, S. (1975) J. Biol. Chem. 250, 9360-9368; McClay, D. R., Wessel, G. M., and Marchase, R. B. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4975-4979). The present results suggest that the cell surface analogs described may provide a well controlled experimental system to probe the molecular events involved in cell-cell adhesion.

Calcitonin gene-related peptide nasal provocation in humans.

Trigeminal sensory nerves release neurotransmitters such as calcitonin gene-related peptide (CGRP), substance P, and others in human nasal mucosa. The effects of CGRP on nasal secretion were tested in humans in vivo by applying CGRP directly to nasal mucosa and then lavaging the nostrils ten minutes later. Concentrations of total protein, albumin, lysozyme, and orcinol-reactive mucoglycoconjugates were measured in lavage fluid. Calcitonin gene-related peptide (0.1 to 100 micrograms) did not stimulate secretion of any of these markers indicating that CGRP had no effect on glandular secretion or albumin exudation in vivo. These findings indicate that CGRP did not stimulate glands or endothelial cells of the vessels that regulate plasma extravasation. These data are consistent with previous studies that demonstrate 125I-CGRP binding sites on arterial vessels without detecting sites on glands or epithelium, the absence of effects of CGRP on glandular secretion from human nasal mucosal explants in vitro, and the apparently minor magnitude of sensory nerve axon responses in humans in vivo.

Adenocarcinoma of the urachus associated with elevated levels of CA 125.

Adenocarcinoma of the urachus is a rare genitourinary tumor with a poor prognosis. The treatment of choice is en bloc surgical resection, although combination therapy with surgery and chemotherapy has been used with mixed results. We describe a 69-year-old woman with adenocarcinoma of the urachus and elevated serum levels of CA 125 tumor marker. She was treated with resection plus 5-fluorouracil, doxorubicin and mitomycin, alternating with platinum-based chemotherapy. The serum CA 125 level decreased precipitously after the operation and became normal after 2 months of chemotherapy. The patient remained free of disease 1 year postoperatively. Serum CA 125 may be a useful tumor marker for urachal carcinoma and adjuvant chemotherapy may be effective in treating the disease.

Tunicamycin inhibits ganglioside biosynthesis in neuronal cells.

The antibiotic tunicamycin blocks the transfer of GlcNAc-1-P from UDP-GlcNAc to dolichol phosphate, thereby blocking the synthesis of N-linked oligosaccharide chains on glycoproteins. Its effect on the biosynthesis of gangliosides has not been reported. We report that tunicamycin caused a 70-80% reduction in incorporation of [(3)H]GlcN into gangliosides and neutral glycosphingolipids of the neuroblastoma-glioma hybrid cell line NG 108-15 at antibiotic concentrations that caused a 90% reduction of the radiolabel incorporation into glycoproteins. The effect of tunicamycin on ganglioside biosynthesis was apparent after only 4 hr of incubation, and maximum inhibition was seen within 6 hr. When control or tunicamycin-treated (5 mug/ml) cells were collected and fractionated to separate glycoproteins, neutral glycosphingolipids, gangliosides, and nucleotide sugar-precursor pools, the following results were obtained: (i) UDP-GlcNAc and UDP-GalNAc pool sizes increased >3-fold, and specific activities decreased 50% upon treatment with tunicamycin; (ii) when corrected for this value, the percentage inhibition of GlcN incorporation into various glycoconjugates by tunicamycin in these cells was 82% for glycoproteins, 54% for neutral glycosphingolipids, and 50% for gangliosides; and (iii) the different gangliosides were affected differentially, with the most striking inhibition apparent in GM(3) biosynthesis, which was decreased 78% in the presence of tunicamycin. These data suggest that the effects of tunicamycin on glycosphingolipids as well as on glycoproteins must be considered when interpreting its effects on intact cells and organisms.

[Clinico-functional evaluation of flunisolide + salbutamol combination (VAL 679/A) vs salbutamol in pediatric patients]. / Valutazione clinico-funzionale dell'associazione flunisolide + salbutamolo (VAL 679/A) vs salbutamolo in pazienti pediatrici.

To establish the effectiveness of flunisolide + salbutamol vs salbutamol alone administered by metered aerosol in the phlogistic obstructive diseases, 18 children were evaluated. The treatments were evaluated on the basis of ventilatory function parameters and of tolerance. The results proved positive for all drugs, though the combination flunisolide + salbutamol produced a greater ventilatory and clinical effect.

In vitro studies of the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects.

The purpose of the present study was to evaluate the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects. Peripheral blood mononuclear leukocytes obtained from five normal subjects and from five patients with allergic rhinitis and asthma were incubated with morphine, ACTH, vasoactive intestinal peptide, or substance P at concentrations of 10(-9) M, 10(-7) M, 10(-6) M and suboptimal (0.0125 microgram/mL, 0.025 microgram/mL, and 0.05 microgram/mL) concentrations of PHA. Uptake of 3H-thymidine was evaluated at 72 hours of culture. An inhibitory effect was observed with morphine, ACTH, and substance P while stimulatory effects were seen with vasoactive intestinal peptide, both in normal and in allergic subjects. The results of these preliminary studies provide further evidence for a modulatory role of neuropeptides on the immune function in both normal and allergic subjects.

Membranous glomerulopathy and chronic small-intestinal enteropathy associated with autoantibodies directed against renal tubular basement membrane and the cytoplasm of intestinal epithelial cells.

A child with an immune-mediated disease is described, who presented two very rare clinical manifestations, a membranous glomerulopathy with circulating anti-renal tubular basement membrane antibody and a small-intestinal enteropathy with circulating antibody directed against the cytoplasm of intestinal epithelial cells. Steroid treatment was followed by complete resolution of the renal but not the intestinal manifestations.

A comparative immunogenicity-reactogenicity dose-response study of influenza vaccine.

This study examined the immunogenic and reactogenic responses of influenza vaccine in 29 healthy nonallergic adults at three vaccine dosages: 0.5 mL, 0.1 mL, and 0.05 mL. After immunization a 7-day assessment of adverse reactions was made and serial serum hemagglutination-inhibition (HAI) antibody responses were measured during a 28-day period. The incidence of adverse reactions was significantly decreased in the group receiving 0.1 mL and 0.05 mL compared with the group receiving 0.5 mL of vaccine. After immunization with 0.1 mL or 0.05 mL vaccine increases in serum HAI antibody to A/Leningrad, A/Taiwan, and B/Ann Arbor influenza antigens were seen comparable to those observed after 0.5 mL. However the magnitude of these rises were lower and were directly correlated with the dose of vaccine. Since immunization of egg-sensitive allergic patients with influenza vaccine poses a risk of localized and systemic reactions, a common clinical practice is to prevent such reactions by vaccine dilution. Although the results of the present study suggest that vaccine dilution results in a decrease in adverse reactions, there is also the risk of decrease protective immunity with this procedure and therefore the practice should not be condoned.