Exploring the intricate links between adenotonsillar hypertrophy, mouth breathing, and craniofacial development in children with sleep-disordered breathing: unraveling the vicious cycle

Adenotonsillar hypertrophy has been well-acknowledged as the primary instigator of sleep-disordered breathing in the pediatric population. This condition spans a spectrum, from typical age-related growth that the immune system influences to persistent pathological hypertrophy. Reduction in air spaces, metabolic changes, neurobehavioral alterations, and chronic inflammation characterizes the latter form. As the go-to treatment, adenotonsillectomy has proven effective. However, it is not a guarantee for all patients, leaving us without reliable predictors of treatment success. Evidence suggests a connection between adenotonsillar hypertrophy and specific oral breathing patterns resulting from craniofacial development. This finding implies an intricate interdependence between the two, hinting at a self-sustaining vicious cycle that persists without proper intervention. The theories regarding the relationship between craniofacial conformation and sleep-disordered breathing have given rise to intriguing perspectives. In particular, the “gracilization theory” and the “gravitational hypothesis” have provided fascinating insights into the complex interaction between craniofacial conformation and SDB. Further investigation is crucial to unraveling the underlying pathophysiological mechanisms behind this relationship. It is also vital to explore the risk factors linked to adenotonsillectomy failure, study the long-term effects of adenotonsillar hypertrophy on craniofacial growth, and devise innovative diagnostic techniques to detect upper airway compromise early. Moreover, to assess their efficacy, we must delve into novel therapeutic approaches for cases that do not respond to traditional treatment, including positional therapy and orofacial myofunctional therapy. Though complex and unpredictable, these challenges promise to enhance our understanding and treatment of adenotonsillar hypertrophy and its related complications in children. By taking on this task, we can pave the way for more effective and targeted interventions, ultimately improving affected individuals’ well-being and quality of life

Chronic toxicity of taurohyodeoxycolic acid in dogs.

Fifty-two-week oral toxicity and 24-week intramuscular toxicity of a new synthetized biliary acid, taurohyodeoxycholic acid (Io, Praxis, CAS 2958-04-5) were investigated in dogs. Taurohyodeoxycholic acid was orally administered at dose levels up to 500 mg/kg/d and i.m. administered at dose levels up to 200 mg/kg/d. No deviations from normality were observed in mortality, physical appearance and general behaviour of the treated animals. Food and water consumption and body weight gain of treated groups did not differ from those of control animals. No treatment-related changes were observed in hematology, serum biochemistry, urinalysis, organ weights and post-mortem macroscopic or histopathological examinations. No dose- or sex-related differences were observed. The no-effect dose level was estimated to be 500 mg/kg/d in the chronic oral toxicity study and 200 mg/kg/d in the intramuscular study

Pharmacokinetics of a Sustained Release Formulation of Pyridoxal Phosphate of Buflomedil After Single or Repeated Oral Doses in Healthy Volunteers.

The pharmacokinetics of a sustained release (SR) formulation of pyridoxal phosphate of buflomedil (Pirxane retard) has been studied after oral administration to healthy volunteers using among else a gaschromatographic dosage method. After oral administration of 400 mg of the SR formulation, pyridoxal phosphate of buflomedil has a much slower kinetics compared to the normal formulation (tmax:approx. 1.5 h) reaching the maximum plasma concentration, which was about 467 ng/ml, in about 3 h. After 24 h the concentrations were still about 1/10 (48 ng/ml) the maximum value. 24-h urinary excretion was about 21% of the administered dose. Repeated administration of the SR formulation for 7 days in single daily doses of 400 mg gave steady state plasma levels (ca. 250 ng/ml) 12 h after the administration without statistically significant variations. The plasma concentrations of the drug measured daily after reaching the steady state were similar one to the other. The tolerability was very good and no local or systemic side effects of any kind were reported

Chronic Toxicity Study on a New Glucan Extracted from Candida albicans in Rats.

Fifty-two-week oral toxicity of a new glucan (Glucanil, Gluimmun) extracted from Candida albicans ATCC 20955 was investigated in rats. The glucan was orally administered in dose levels up to 200 mg/kg/d and was well tolerated. No deviation from normality was observed in mortality, physical appearance and general behaviour of the treated animals. Food and water consumption and body weight gain of glucan-fed groups did not differ from those of control animals. In these groups no alteration of the weight of the main organs was also observed. Hematology, blood chemistry, urinalysis and autopsy findings were within normal ranges in every group of rats treated. No sex difference was noted. In the 200 mg/kg group soft stools or diarrhoea and cecal enlargement with variable hyperplasia of the colon mucosa were observed. These symptoms are typical of exposure to substances which are absorbed incompletely in the small intestine and subjected to microbial metabolism in the cecum and colon. Diarrhoea, cecal enlargement and mucosal hyperplasia are reversible. The no-effect dose level was estimated to be 100 mg/kg/d under these conditions

Lack of influence of sulglycotide on naproxen bioavailability in healthy volunteers.

We explored the bioavailability and kinetics of naproxen (N) in 12 healthy volunteers treated orally with single doses of 500 mg and retreated after a washout period with the same dose of N plus sulglycotide (S) 200 mg. Naproxen blood levels were measured by high-performance liquid chromatography (HPLC) in samples collected at 0.5, 1, 2, 4, 8, 12, and 24 h of dosing with N or with N + S. No statistically significant difference in terms of naproxen blood levels emerged as the product was administered alone or concurrently with sulglycotide. Peak plasma concentrations and AUC values were 71 +/- 3.16 micrograms/ml and 685 +/- 27 micrograms/ml/h, respectively for N alone, and 72.5 +/- 2.85 micrograms/ml and 651 +/- 28 micrograms/ml/h, respectively for N + S. The difference was not significant. Similarly, the kinetic behavior of naproxen was not modified by the simultaneous presence of sulglycotide, as shown by the t1/2 beta-values obtained with N alone (8.39 +/- 0.31 h) and with N + S (7.93 +/- 0.30 h), and likewise by the distribution volumes at equilibrium (7.63 +/- 0.42 and 7.9 +/- 0.38, respectively), Cmax (63.3 +/- 2.86 and 60.4 +/- 2.9 micrograms/ml, respectively) and tmax (0.95 +/- 0.06 and 1.10 +/- 0.10 h, respectively). From these findings it seems legitimate to claim that sulglycotide can be administered concurrently with naproxen to prevent possible gastric injury by the anti-inflammatory agent thanks to its wellknown antiulcer and cytoprotective activity on the gastric mucosa, without any undue interference with the absorption (hence effectiveness) of naproxen

Lack of effect of a single-dose of sulglicotide on the bioavailability of diclofenac.

The bioavailability of diclofenac (D) was assessed in 12 healthy volunteers treated orally with single doses of 100 mg (retard formulation) and subsequently retreated with the same dose of (D) plus sulglicotide (S) 200 mg. (D) blood levels were measured by GLC in samples collected after 1, 2, 4, 6, 8, 12, 24 h. No relevant difference was seen in (D) bioavailability after (S) administration; after 8 h plasma levels of (D) were slightly higher after (S) (p less than 0.05), but this difference can be considered incidental only. Thus, sulglicotide does not interfere with the bioavailability of diclofenac, and can be administered concurrently with the latter to prevent possible gastric injury by the antiinflammatory drug

Bioavailability of oral N-acetylcysteine as suckable tables in man.

The pharmacokinetics and bioavailability of suckable tablets and granules of N-acetylcysteine (NAC) have been compared after oral administration of 400 mg doses to 10 healthy volunteers. The oral bioavailability of the NAC tablets was 103%. In a multiple dosing study of the same tablets in the same subjects, a high maintenance plasma level of NAC was revealed