Active principle of swine prostate extract: I. Isolation of active principle activating prostatic acid phosphatase and its effect on testosterone uptake of the prostate in castrated rats

There have been several reports concerning the therapeutic effect of an extract from animal prostates on benign prostatic hypertrophy. Previously, we reported that the swine prostate extract (PE) had the activity to enhance human prostatic acid phosphatase (PAPase) activity in vitro, and to increase the muscular tonicity of the urinary bladder by directly acting upon vesical muscles, suggesting that PE have an activity to elevate the intravesical voiding pressure in vivo. In the present study, it was attempted to isolate such an active principle of PE as activates human prostatic acid phosphatase (PAPase). The finally purified PE (PPE) was assessed as to some physico-chemical and pharmacological properties. 1) PPE was found to be a peptide with a molecular weight of about 8,800, composed largely of neutral amino acids (approximately 70%) and few of aromatic amino acids. 2) PPE activated PAPase in a dose-dependent fashion, resulting in an increase of the enzyme activity approximately twice in a dose of 2 X 10(-5) g/ml of PPE. Furthermore, PPE recovered PAPase activity dose-dependently from the 50% inhibition by 2 X 10(-3) M L-tartaric acid. 3) In castrated rats, the 3H-testosterone uptake of the prostate was significantly suppressed by the oral administration of PPE. PPE might be one of active principles of PE for the therapeutic effect on prostatic hypertrophy.     

Effect of three novel K+ channel openers, cromakalim, pinacidil and nicorandil on allergic reaction and experimental asthma.

The anti-allergic and anti-asthmatic activities of three potassium (K+) channel openers, cromakalim, pinacidil, and nicorandil, were investigated. 1) Forty-eight-hour homologous passive cutaneous anaphylaxis (PCA) in mice was not affected by cromakalim, pinacidil, or nicorandil. Ketotifen significantly inhibited the reaction. 2) Antigen-induced histamine release from sensitized guinea pig lung tissue was not affected by cromakalim, pinacidil or nicorandil (except for 10(-4) M nicorandil). Salbutamol inhibited the release of histamine. 3) Histamine, serotonin and LTC4-induced vasculitis in rat back skin was not affected by any of these three K+ channel openers. 4) Antigen-induced constriction of isolated sensitized guinea pig tracheal muscle was relaxed by each of the K+ channel openers. 5) Constrictions of isolated guinea pig tracheal muscle caused by high potassium, histamine, LTC4, or U-46619 were clearly relaxed by each of the three K+ channel openers. 6) Increases of airway resistance caused by histamine, LTD4, or U-46619 in guinea pigs in vivo were inhibited by administration of each of the three K+ channel openers. 7) Experimental asthma caused by the IgE antibody and antigen system in guinea pigs was inhibited by each of the three K+ channel openers.     

Stability of irinotecan hydrochloride in aqueous solutions.

The stability of irinotecan after reconstitution in several vehicles for i.v. infusion was studied. Irinotecan hydrochloride injection was diluted in phosphate buffer solution (pH 4.0, 6.0, and 7.4), 5% dextrose injection, and 0.9% sodium chloride injection to a final concentration of 20 micrograms/mL. The solutions were stored at 25, 37, and 50 degrees C and assayed at intervals up to 24 hours by high-performance liquid chromatography for the concentration of the lactone form of irinotecan remaining. The effect of temperature and pH on the extent and rate of degradation of irinotecan was determined. The hydrolysis of irinotecan to its carboxylate form was reversible. The rate and extent of hydrolysis increased with increasing pH. The use of a weakly acidic vehicle, such as 5% dextrose injection, for reconstitution of irinotecan may maintain the drug's stability prior to administration.     

Hepatic vascular and bile duct injury after ethanol injection therapy for hepatocellular carcinoma

Three patients with serious hepatic vascular injury after percutaneous ethanol injection therapy for hepatocellular carcinoma (HCC) are described. In two cases, immediately after ethanol injection, liver function tests deteriorated and computed tomography (CT) showed a wedge-shaped low-density area due to liver infarction. In the other case, 1 year after ethanol injection, the intrahepatic bile duct in the right lobe was dilated and the right hepatic lobe atrophied. Endoscopic retrograde cholangiography showed stenosis of the main right hepatic duct. Since complications include both acute and delayed vascular injury after ethanol injection, patients should be followed for a long period after treatment.     

Clinical assessment of monoclonal antibodies for the treatment and diagnosis of colorectal cancers

The clinically useful monoclonal antibodies(Mabs) for colorectal cancers were reviewed. Since 1980's, immunoscintigraphy has been performed for the detection of occult colorectal cancers. However, it may be substituted with the development of positron emission tomography. As for the treatment, some Mabs have been shown to be effective for the adjuvant therapy of postoperative colorectal cancers. Some Mabs to epidermal growth factor receptors(EGFr) are quite promising since they block the functions necessary for the tumor growth and enhance the cytotoxicity of chemotherapy. Recent advances for the development of humanized Mabs will improve the chance of Mabs to be used as an effective adjuvant.     

Surgical simulation of circumferential osteotomy and correction of cervico-thoracic kyphoscoliosis for an irreducible old C6–C7 fracture dislocation

Background  Many different surgical procedures have been employed in the treatment of fracture dislocation at the middle to lower cervical spine. However, consistent protocols and procedures have not been fully established for the surgical correction of an irreducible old cervical fracture dislocation associated with spinal deformity. Methods  We report a case of irreducible cervical fracture dislocation and kyphoscoliosis, in which surgical simulation using a three-dimensional full-scale model was useful for circumferential corrective osteotomy at the C6–C7 level. A 56-year-old man was diagnosed with an irreducible fracture dislocation at the C6–C7 level 2 months after a motor vehicle accident. He showed torticollis, and complained of severe pain in his neck and left upper arm. Radiographic examinations revealed that the C6 vertebra was translated anteriorly and laterally to the C7 vertebra. A bony union had progressed at the fracture site, showing rigid cervico-thoracic kyphoscoliosis. To assist in the preoperative planning, we created a three-dimensional, full-scale model from the patient's computed tomography data. Using the model, we performed a simulation of the planned circumferential corrective osteotomy at the C6–C7 level. Results  Through the simulation, we could evaluate the deformed bony structures around the vertebral arteries at the C6–C7 level accurately. At the time of the actual surgery, corrective osteotomy combined with spinal fusion (C5–T2) with a pedicle screw-rod system was accomplished successfully without any neurovascular complications. After surgery, the patient experienced relief from pain, and his neck posture became normal. Conclusions  Surgical simulation using a three-dimensional, full-scale model was useful for improving the accuracy and safety of circumferential corrective osteotomy of the cervical spine.