The Effects of Combined Intravenous and Inhaled Steroids (Beclomethasone Dipropionate) for the Emergency Treatment of Acute Asthma

Objective : To compare the efficacy of high-dose inhaled steroids in conjunction with IV steroids with that of IV steroids alone in the emergency treatment for acute asthma.
Methods : A double-blind, placebo-controlled, randomized trial was conducted on 60 ED patients presenting with acute asthma. All patients received nebulized salbutamol, and IV methylprednisolone, 80 mg at baseline and 40 mg at 6 hours. In addition to the above therapy, the experimental group received beclomethasone dipropionate (BDP) 7 mg over 8 hours via a metered-dose inhaler (MDI) attached to a holding chamber, while the control group received a placebo administered in the same fashion. Patients were treated on the protocol for 12 hours with the primary outcome measure being the change in % predicted FEV₁.
Results : Of 60 patients, 30 were randomized to BDP (age: 42 ± 16 years; FEV₁: 0.97 ± 0.42 L) and 30 were randomized to placebo (age: 37 ± 18 years; FEV₁: 0.98 ± 0.35 L). Spirometry and dyspnea measured by the Borg Scale improved significantly in both groups compared with baseline (p < 0.001). Changes in spirometry measures, dyspnea, and vital signs did not differ between treatment groups over the 12 hours of study (p > 0.05).
Conclusion : Inhaled BDP added to the standard regimen of IV methylprednisolone, and β-agonist did not further improve flow rates or dyspnea scores measured for up to 12 hours after presentation to the ED.     

An inhibitory effect of veratridine during tetanic stimulation of the rat diaphragm

The membrane ‘labilizer’ veratridine (3.7 ± 10^-6 m) which potentiates the contractions at twitch (0.1 Hz) stimulation due to multiple discharges, inhibited the tetanic contractions (50 Hz in 10 s) and the simultaneously recorded electromyogram in a use-dependent way, leading to fading of tetanic tension. The effect was equal during indirect and direct stimulation, and could therefore be localized to the excitable sarcolemma. This was confirmed by intracellular recording of action potentials, showing a marked veratridine-induced fallout of action potentials during continuous 50 Hz stimulation, whereas endplate potentials were unaffected. Accordingly, veratridine probably caused a use-dependent inhibition of the Na⁺ channels of the excitable sarcolemma. The tetanic fade was unaffected by K⁺ depolarization, increased by hyperpolarization in K⁺-free solution, and decreased by high Ca²⁺. All these changes of the ionic concentrations inhibited the twitch potentiating effect of veratridine. Since hyperpolarization and increasing the electric field in the membrane with high Ca^,+ had opposite effects on the tetanic fade, the field change was probably not the cause of the antagonism in high Ca²⁺. Instead, a membrane stabilizing effect of high Ca²⁺ is suggested, since the neutral local anaesthetic benzocaine (1.5 ± 10^-4 m), which is also a membrane stabilizing drug, had the same effects as high Ca²⁺ on the veratridine-induced tetanic fade. The effect of veratrine during tetanic stimulation was partly reversible upon washing. The reversibility was enhanced by high Ca²⁺ or benzocaine.     

Magnetic resonance imaging of cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis is a rare familial sterol storage disease with accumulation of cholestanol and cholesterol particularly in xanthomas, bile and brain. Magnetic resonance imaging is a useful modality for imaging the affected tissues. It contributes to the evaluation and management of the disease.     

Nuclear magnetic resonance studies on the interaction of avoparcin with model receptors of bacterial cell walls

On the basis of nuclear Overhauser enhancement and 1H chemical shift data obtained in aqueous solution, a model is proposed for the interaction of beta-avoparcin and epi-beta-avoparcin with acetyl-D-alanyl-D-alanine (Ac-D-Ala-D-Ala) and diacetyl-L-lysyl-D-alanyl-D-alanine (Ac2-L-Lys-D-Ala-D-Ala). For the beta-avoparcin: Ac2-L-Lys-D-Ala-Ala complex, the COOH-terminal end of the tripeptide is located near the NH2 terminus of the antibiotic with the tripeptide extending across the peptide backbone of beta-avoparcin toward its COOH-terminal end. In our proposed structure, the three amino acid residues of the peptide span the entire length of the antibiotic, and the aliphatic side chain of the lysine residue extends over the D-ring of beta-avoparcin. The structure of the epi-beta-avoparcin:Ac2-L-Lys-D-Ala-D-Ala complex was found to be similar to the beta-avoparcin complex at the binding site for the lysine residue at the COOH-terminal end of the antibiotic, but differed in the interactions at the NH2 terminus. These results are consistent with the similarities in the COOH-terminal conformations and the differences in conformations at the NH2 terminus found for beta-avoparcin and epi-beta-avoparcin which were described in the preceding paper [Fesik, S. W., I. M. Armitage, G. A. Ellestad, and W. J. McGahren, Mol. Pharmacol. 25:275-280 (1984)]. The association constants (measured by UV methods) for both beta-avoparcin:peptide complexes were greater than those measured for epi-beta-avoparcin and correlated with their differences in antibacterial activity. Epi-beta-avoparcin exhibited no measurable binding to the dipeptide: however, a significant affinity was measured for the tripeptide, indicating that the interactions with the NH2 terminus of the antibiotics provide binding energy for the antibiotic peptide complex but that the COOH-terminal end of the antibiotics also plays an important role in the binding interaction. These results are interesting in light of the similarities in the structural and conformational features at the COOH terminus for all of the glycopeptide antibiotics.