A review on the development of Kallikrein (Kallidinogenase)

This article briefly summarizes the historical events particularly these in Japan, in the kallikrein-kinin research and progress of the development of kallidinogenase (INN), enzyme with circulatory action. In 1926, E. K. Frey observed a drop in blood pressure in dogs following intravenous injection of the urine of human and other mammals into dogs. Intensive research showed that the urine contained a high-molecular active substance which dilated the peripheral arterial vessels. The substance was later called kallikrein after the Greek synonym for pancreas, as it occurred there at such a high concentration (Kraut et al., 1930) that this gland was thought to be its cite of origin. In 1930, kallikrein was commercially available as Padutin from Bayer, Germany. The product was introduced into Japan a few years later under the trade name of Kallikrein and was used for the treatment of circulatory disorders even during the Second World War. Kallikrein was again imported by Yoshitomi Pharmaceutical Industries, Ltd. in 1952. However, Kallikrein introduced after the War did not contain substance derived from the urine but from porcine pancreatic kallikrein as the active ingredient. It grew rapidly with its active promotion of the product in such fields as internal medicine, ophthalmology, otology etc. Domestic manufacturers increasingly entered this market and the number of the manufacturing license holders of similar products reached 26 in 1975 when kallidinogenase preparations were designated to undergo drug re-evaluation by the health authorities. Since June 1988 when the re-evaluation for kallidinogenase preparations was completed, all the relevant manufacturers have supplied new formulations containing higher quality substances and labeling their potencies expressed in International Units based on the kallidinogenase reference standards which had since been established.     

Analysis of C-myc messenger-RNA expression in primary breast carcinomas with clinical follow-up

The level of c-myc messenger RNA was measured in 105 primary breast carcinoma samples and matched normal breast tissue from the same patients. Only tumors showing a greater than 2-fold increase in c-myc levels were considered to be overexpressed. Overexpression of c-myc mRNA was identified in 27.6% of tumor samples analysed and was significantly correlated with mitotic grade (p=0.05) and intense lymphocytic infiltrate (p=0.026) but not with other clinical and pathological variables such as size, necrosis, lymph node involvement, estrogen or progesterone receptor status, menopausal status, age or staging of the patients and increased risk of relapse or overall survival. Approximately 25% of the tumors contained overexpression of c-erbB-2 mRNA and simultaneous overexpression of the two oncogenes was seen in only five samples. Disease-free survival was significantly shorter in these patients (p=0.02) and this reduction remained significant after adjustment for nodal status. However, simultaneous overexpression of c-myc and c-erbB-2 did not improve significantly the prediction of risk of death.     

A short history of patient package insert in the EU

In recent years the Japanese general public has become increasingly aware of health matters, and many people wish to know more about the medicines they receive from doctors. This means that Japanese patients have not been given medicinal product information fully by medical professionals, whereas many European countries have already introduced patient package inserts (PPIs) with near full disclosure leaflets in understandable language in all packages of dispensed medications. This article describes a short history of PPIs in European countries, centering on the development of PPIs in Germany and Belgium. It is expected that these European experiences contribute to our country in terms of providing patients with pharmaceutical information.     

Health status of male preparatory school students lodging at a dormitory in Japan

An investigation on the health status of 79 male preparatory school students lodging at a dormitory in Japan was carried out by questionnaire on lifestyles, subjective symptoms and mental status, as compared with two control groups: 73 medical students and 36 new employees. About 83 % of them slept less than 6 hours and 70 % of them did not exercise. Many students are troubled with back pain or lumbago(47%), sensation of incomplete bladder emptying(l6%), loss of visual acuity(55%) and eye fatigue(65%). Self-rating depression scale score of preparatory school students was not significantly higher than those of the control groups. The lifestyles of preparatory school students found to be very restricted and strained. However, no significant differences on mental adverse health effects was found among three groups.     

A case of retroperitoneal hemangiopericytoma

We report a case of a huge retroperitoneal tumor in a 67-year-old woman. When the patient was taken to another hospital by ambulance, she had lost consciousness because of hypertension and hypoglycemia and abdominal CT revealed a huge retroperitoneal tumor with deviation of the right kidney and inferior vena cava. After further examinations including ultrasonography, MRI and angiography in our hospital, the tumor was extirpated. The tumor, 22 x 17 x 10 cm in size and 2,580 g in weight was diagnosed as hemangiopericytoma histologically. She has remained well with no evidence of recurrence for 9 months since the operation.     

Comparison of the axonal and glial reactions between the caudal and rostral border in the cryoinjured dorsal funiculus of the rat spinal cord

Axonal and glial reactions to traumatic injury were compared between the caudal and rostral border of the lesion after freeze-injury to the C3 dorsal funiculus by attaching a liquid nitrogen-cooled copper probe to the dorsum of the rat spinal cord. The axonal and glial changes were examined up to 60 days postoperative by light and electron microscopy and immunohistochemistry for neurofilaments. Regenerative axonal changes and the appearance of numerous undifferentiated cells were found at the caudal border 7 days after cryoinjury. In contrast, such axonal and cellular reactions were scarce at the rostral border. Undifferentiated cells clearly manifested their phenotypes by differentiating into oligodendrocytes or astrocytes 11 days postinjury. The results indicated that glial cell reactions occurred in association with regenerative axonal changes at the proximal stump of the injured nerve fibers, suggesting that regenerating and demyelinated naked axons could be responsible for the appearance of the immature glial cells.     

Absorption and distribution of lycopene in rat colon.

Colonic absorption and distribution of lycopene, which inhibited rat colon carcinogenesis in our previous studies, were investigated in Sprague-Dawley rats. Three groups of six rats each with or without a single-barreled colostomy at the mid colon were given a single intragastric or intracolonic dose of 0.2 mL of corn oil containing 12 mg of lycopene. Twenty-four hours later, all rats were sacrificed and the blood and some tissues were collected. The contents of lycopene in the samples were assayed by HPLC. Lycopene was detected in an appreciable amount in the liver, but only in trace amount in the serum of all rats treated with an intracolonic dose of lycopene and in rats with an intragastric dose. After an intragastric lycopene treatment, lycopene was detected in the mucosa of the proximal colon and of the distal colon of the colostomized rats, whose distal colon had been excluded from the fecal stream. A large amount of lycopene was recovered in the feces. None was detected in any sample from the control rats treated with an intragastric or intracolonic dose of plain corn oil. The results suggest that lycopene is absorbed from the colon and also from the small intestine. It might be concluded that both ways of absorption contribute to a comparative amount of lycopene accumulation in the colon mucosa after ingestion of this carotenoid.     

Jatamols A and B: Sesquiterpenoids of Nardostachys jatamansi Roots1

From the roots and rhizomes of NARDOSTACHYS JATAMANSI, two new eudesmanes jatamols A and B were isolated, and their structures were determined by spectral analysis and chemical evidence.