Intrathecal injection of a specific enzyme in rats as a model for chemically induced spinal cord injury

A spinal cord injury model is described using chymopapain as a neurotoxic agent in rats. The trauma was evaluated by neurophysiological and morphological methods. Electrically evoked compound action potentials were used to quantify the neurophysiological effects caused by the injection of chymopapain into the lumbar dural theca in rats. A branch of the sciatic nerve was stimulated with voltage impulses of constant amplitude (40 V) and duration (0.1 ms) at the right external malleolus. The responses were recorded at the dorsal root entry zone L1. We used different doses of the enzyme (1000 i.u./ml; 2500 i.u./ml; 5000 i.u./ml). A total amount of 0.1 ml was injected into the rats' lumbar spinal canal intrathecally (n = 18). The control rate (n = 8) were subjected to exactly the same stimulus and recording procedures but the test solution was a corresponding volume of isotonic saline. Two hours after injection the animals were examined clinically and then sacrificed for histology. The prolongation of the latency of the electrically evoked potentials caused by the enzyme was very clear at the doses of 2500 i.u. and 5000 i.u. being about 10-15% relative to the mean latency before administration of the drug. The histological evaluation showed hemorrhage, vascular damage and indirect signs of myelin edema of the lumbar nerve tissue. Our study indicates that chymopapain injections into the lumbar spinal canal can be used as a reproducible model for spinal cord injury research.     

Clinical applications of mifepristone.

Mifepristone is a progesterone antagonist that has been studied for a number of clinical applications. It is a well-known abortifacient that is effective for both first- and second-trimester medical abortion when used with a prostaglandin analog. It is also an effective cervical priming agent that can be used to soften the cervix before surgical evacuation. Its clinical efficacy as an emergency contraception has been proven. Other applications including treatment for fibroids, endometriosis and various cancers have been explored. However, its association with abortion limits the applications of mifepristone in many of these areas.     

Effect of meal on the physiological and physicochemical actions of potassium citrate

The effect of meals on the physiological and physicochemical actions of potassium citrate was examined in 8 patients with nephrolithiasis maintained on a constant metabolic dietary regimen. Potassium citrate (20 mEq. 3 times per day), whether given with food or on an empty stomach, significantly increased urinary pH, citrate and potassium, and decreased urinary calcium and ammonium. Moreover, potassium citrate decreased urinary saturation of calcium oxalate and uric acid, although it slightly increased that of brushite. However, there was no significant difference in these measures when the drug was given with meals from the time when it was given on an empty stomach. Thus, the effect of potassium citrate on urinary risk factors is unaffected by food.     

Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats.

Recent studies have revealed that the phosphatidylinositol 3-kinase (PI3-K) pathway is involved in apoptotic cell death after experimental cerebral ischemia. The serine-threonine kinase, Akt, functions in the PI3-K pathway and prevents apoptosis by phosphorylation at Ser473 after a variety of cell death stimuli. After phosphorylation, activated Akt inactivates other apoptogenic factors, including glycogen synthase kinase-3beta (GSK3beta), thereby inhibiting cell death. However, the role of Akt/GSK3beta signaling in the delayed death of hippocampal neurons in the CA1 subregion after transient global cerebral ischemia (tGCI) has not been clarified. Transient global cerebral ischemia for 5 mins was induced by bilateral common carotid artery occlusion combined with hypotension. Western blot analysis showed a significant increase in phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) in the hippocampal CA1 subregion after tGCI. Immunohistochemistry showed that expression of phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) was markedly increased in the vulnerable CA1 subregion, but not in the ischemic-tolerant CA3 subregion. Double staining with phospho-GSK3beta (Ser9) and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed different cellular distributions in the CA1 subregion 3 days after tGCI. Phosphorylation of Akt and GSK3beta was prevented by LY294002, a PI3-K inhibitor, which facilitated subsequent DNA fragmentation 3 days after tGCI. Moreover, transgenic rats that overexpress copper/zinc-superoxide dismutase, which is known to be neuroprotective against delayed hippocampal CA1 injury after tGCI, had enhanced and persistent phosphorylation of both Akt and GSK3beta after tGCI. These findings suggest that activation of the Akt/GSK3beta signaling pathway may mediate survival of vulnerable hippocampal CA1 neurons after tGCI.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Assessment of bronchodilator response to a beta-adrenergic delivered from an ultrasonic nebulizer

We assessed the bronchodilator response to a recently available ultrasonic nebulizer (USN) in a population of 17 stable asthmatic patients. These patients were also evaluated for bronchodilator response to two other aerosol delivery systems routinely used in standard clinical practice, the metered-dose inhaler (MDI) and the jet nebulizer (JN). Albuterol was administered from each of the delivery systems in the following manner: MDI, two actuations (180 micrograms); JN, 0.5 ml of 0.5 percent solution (2.5 mg) in 1.0 ml saline solution diluent; and USN, 0.5 ml of 0.5 percent solution (2.5 mg) in 2.5 ml saline solution diluent. Patients demonstrated significant bronchodilator responses to all three delivery systems (p less than 0.0001). The USN produced a greater percentage of increase in FEV1 15 minutes after treatment with albuterol (35.8 +/- 2.3 percent) than either the MDI (18.2 +/- 3.4 percent) or JN (20.8 +/- 3.1 percent) (p less than 0.005). The mean percentage of increase in FE1 observed over a 4-h period after treatment was also greater for the USN (26.5 +/- 2.5 percent) than either the MDI (18.8 +/- 1.8 percent) or JN (15.0 +/- 1.6 percent) (p less than 0.001). We conclude that the USN yields effective bronchodilation in a population of stable asthmatics.     

A study on the hemodialysis period following cadaveric kidney transplantation--a comparison between two centers sharing cadaver donor kidney pairs

To study the hemodialysis period following cadaveric renal transplantation, we reviewed 18 consecutive cadaver donor kidney pairs of which one kidney was transplanted at Shiga University of Medical Science (SUMS) while the contralateral kidney was transplanted at Kyoto Prefectural Medical University (KPMU) between January 1983 and September 1988. Of these 18 pairs, graft function was satisfactory and the recipient was free from hemodialysis in 13 pairs. However, the postoperative hemodialysis periods were different between the two centers. To clarify the factors causing this difference, recipient factors, such as age, HLA matching, total ischemic time of the graft (TIT), immunosuppression, onset of diuresis and postoperative complications were studied. There were no significant differences in age, HLA matching, or immunosuppression. TIT of cases at SUMS was significantly longer than that of cases at KPMU. The postoperative hemodialysis period at SUMS was 25.8 days and that at KPMU was 17.8 days, however, the difference was not statistically significant. The results of this study indicate that TIT seems to be a major factor relating to delayed graft function in cadaveric renal transplantation.     

Free-radical oxidation of blood plasma lipids in patients with acute intestinal infections

Blood plasma free radical lipid oxidation was studied in 98 patients with acute dysentery (AD) and 64 patients with food toxinfection (FTI). Free radical lipid oxidation was assessed by the intensity of chemiluminescence and the level of lipid peroxides. Activation of blood plasma lipid peroxidation was established with relation to a clinical variant of the disease. The effect of indomethacin on the parameters of free radical lipid oxidation was noted in patients with AD and FTI.