Mucoadhesive Microspheres Containing Amoxicillin for Clearance of Helicobacter pylori

In an effort to augment the anti-Helicobacter pylori effect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared. The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension. The in vivo clearance of H. pylori following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions. The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-H. pylori effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres more effectively cleared H. pylori from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion. A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of H. pylori.     

Simulation for population analysis of Michaelis-Menten elimination kinetics

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug. This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.     

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.     

Development of the brainstem: assessment by MR imaging

The morphological development of the brainstem was studied by means of MR imaging. The subjects were 74 cases ranging in age from 4 months to 16 years, and 6 adult cases. The brainstem development was rapid until 4-6 years of age and thereafter it slowed down. That is the brainstem showed exponential growth (w', t', v and u). The relationship between brainstem growth and the cranium size was divided into 4 types as follows: 1) linear increase with development (s/T-O), 2) plateau (w/T-I and v/RTP-LTP), 3) down and up (u/RTM-LTM and z/RTM-LTM) and 4) exponential (t/T-P). In the values of v, z (the size of the brainstem in axial view) and t/T-P (the ratio of the midbrain and the cranium size in sagittal view), there were significant sex differences for cases of 10-16 years old. These values in male subjects were greater than those in female subjects (v, p less than 0.05, z, p less than 0.01, and t/T-P, p less than 0.05). That is the brainstem in male subjects was greater than that in female subjects.     

Primary brain stem lesions caused by closed head injuries

Traumatic lesions of the brain stem are of two types: primary, which are considered to be caused at the moment of impact, and secondary, associated with supratentorial mass lesion. Of the 239 patients with a serious head injury who showed a severe disturbance of consciousness upon admisision and who had CT scan carried out immediately, 21 cases were considered to have a primary brain stem lesion with initial CT scan. A primary brain stem lesion was found in 21 of 239 (8.8%) of patients with serious head injury. Their injuries were caused primarily by traffic accidents. Sixteen of the 21 cases showed not only brain stem lesions but also other brain injuries such as cerebral contusion of the white and gray matter, callosal injury, intraventricular hemorrhage, and subarachnoid hemorrhage, which are considered to be caused by a diffuse shearing injury. Five cases who showed a single injury to the brain stem with no other brain lesions were considered to have a pure brain stem lesion. Primary brain stem lesions were observed on the dorsal side of the midbrain, where they can be differentiated from secondary brain stem lesions. These lesions are considered to result from the shearing mechanism in and around the brain stem very close to the tentorial edge, or to an injury of the lower brain stem by hyperextension of the cervical vertebrae. The prognosis of patients with a primary brain stem lesion was usually unfavorable, except in those with a single brain stem lesion.     

Autoperfusion balloon catheter for treatment of vertebral artery stenosis

Percutaneous transluminal angioplasty (PTA) of the vertebral artery was performed with an autoperfusion balloon catheter in five patients. There were no complications in the form of embolic episodes or neurological deficits due to brain ischaemia during inflation. In critical cases with insufficient collateral circulation during temporary occlusion, the use of an autoperfusion balloon catheter may expand the indications for PTA in patients with ischaemic cerebrovascular disease.     

Effects of isoflurane on oxygenation during one-lung ventilation in pulmonary emphysema patients

Background: Hypoxic pulmonary vasoconstriction has an important role in human one-lung ventilation (OLV) in the lateral decubitus position under general anesthesia. During OLV, inhalational anesthesia may inhibit hypoxic pulmonary vasoconstriction and the decrease in arterial oxygenation. We studied the effect of isoflurane administration on arterial oxygen tension in chronic obstructive pulmonary disease patients.
Methods: Ten patients who had thoracoscopic laser ablation of bullous emphysema were studied. Patients received 2% isoflurane in oxygen from induction until the first 20 min of OLV in the lateral decubitus position, then were switched to 1% isoflurane lasting 20 min and next were switched to 0.5% isoflurane lasting 20 min. After each 20-min inhalation, pulmonary and hemodynamic parameters were measured. The given concentrations for isoflurane were merely vapor meter concentrations.
Results: PaO₂/FIO₂, Qs/Qt respiratory rate peak inspiratory pressure and PaCO₂ showed no significant changes at each point of isoflurane. Expiratory tidal volume significantly decreased (P<0.05) with 0.5% isoflurane compared to that with 2% isoflurane. Cardiac output, mean arterial pressure, mean pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance showed no significant changes at each point of isoflurane.
Conclusions: In patients with pulmonary emphysema, arterial oxygenation is not affected by low isoflurane concentration during OLV in the lateral decubitus position.