Induction of Cytotoxic Cell Activities by a Novel Cyclic Disulfide Compound, SA3443 in vivo

(4R)-Hexahydro-7, 7-dimethyl-6-oxo-1, 2, 5-dithiazocine-4-carboxylic acid (SA3443) is a newly synthesized cyclic disulfide compound which offers potential hepatoprotective properties.

The effect of SA3443 on the induction of natural killer (NK) and cytotoxic T lymphocyte (CTL) activities was investigated. NK activity in BALB/c mice splenic cells was investigated using YAC-1 cells as target cells. SA3443, at a dose range of 30-300 mg/kg/day, augmented NK activity significantly when administered orally once daily for 4 days before the assay. Alloantigen-specific CTL activity in splenic cells from BALB/c mice was detected 9 days after sensitization with C57BL/6 mice splenic cells. SA3443, at a dose of 100 mg/kg/day, augmented CTL activity significantly when administered orally, once daily for 4 days beginning after the sensitization and for 2 days before the assay, while a high dose of SA3443, at 300mg/kg, suppressed CTL activity.

From these results, it is thought that SA3443 may assist in the elimination of hepatitis viruses from the liver in patients with chronic active hepatitis, by the activation of NK and/or CTL activities.     

Large Ulcerated Perianal Hidradenoma Papilliferum in a Young Female

BACKGROUND: Hidradenoma papilliferum is an uncommon benign tumor that is located almost exclusively in the vulvar and anal areas. It is usually very small and asymptomatic, and to make a correct diagnosis is clinically very difficult. Occasionally the tumor becomes elevated to form a reddish brown papillary mass, and the surface ulcerates, which may erroneously suggest malignancy. OBJECTIVE: We report a case of a large, perianal hidradenoma papilliferum with suspected malignancy in a young Japanese female. RESULTS: A 22-year-old female had been aware of a perianal nodule for approximately 1 year. Examination of the perianal area revealed a wide pedunculated, reddish nodule with several white maculae. It was ulcerated and bleeding, 2.0 x 1.2 x 0.8 cm in size, and located in the 3 o'clock position. The nodule was totally excised with a narrow margin. The histopathologic diagnosis was hidradenoma papilliferum. No recurrence was observed for 23 months. CONCLUSION: When dermatologists encounter tumors of the anogenital area of adult females, it is important to keep hidradenoma papilliferum in mind as the differential diagnosis. Dermatologists should recognize that the tumor is benign, eliminating the need for wide resection.     

Modification of the Na,K-pump of glial cells within cobalt-induced epileptogenic cortex of rat

The characteristics of a glial Na⁺,K⁺-pump dependent on extracellular K⁺ within epileptogenic cortex were studied electrophysiologically, biochemically and histochemically in vitro using slices from cobalt-induced epileptogenic cortex of rat. When the extracellular K⁺ concentration ([K⁺]_o) was varied between 4 and 40 mM, the mean slope of membrane potential plotted against [K⁺]_o was about 57 mV in glia from the normal cortex (tissue A) and about 44 mV in glia from the epileptogenic cortex (tissue B); whereas no significant difference in the resting membrane potential of these tissues was observed. In glia from tissue B, a marked transient hyperpolarization above control level was caused by replacement of elevated [K⁺]_o with the normal medium. Ouabain abolished these phenomena observed in glia from tissue B, but had no effect on the membrane potential during normal [K⁺]_o. Reduction of extracellular Na⁺, Ca²⁺ and Cl⁻ did not significantly affect the membrane potential of glia from either tissue. In tissue A, the cells marked by intracellular injection of horseradish peroxidase after intracellular recording were protoplasmic astrocytes; in tissue B, fibrous astrocytes with abnormal processes predominated. K⁺-dependent stimulation of Na⁺,K⁺-ATPase activity of the astrocyte-enriched fraction and its membrane preparation from tissue B was much larger than that from tissue A. A certain amount of the reaction product of K⁺-pNPPase activity was seen on glial plasma membrane within tissue B but not on that from tissue A. The above findings suggest that a glial Na⁺,K⁺-pump within actively firing epileptogenic cortex may be modified to increase in its activity.     

Low-molecular-weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers

Biodegradable copolymers of L -lactic acid (L -LA) and DL -α-hydroxy acids with relatively low molecular weights, for example L -LA/DL -lactic acid (DL -LA), L -LA/DL -α-hydroxybutyric acid (DL -HBA), L -LA/DL -α-hydroxyisovaleric acid (DL -HIVA), and L -LA/DL -α-hydroxyisocaproic acid (DL -HICA), were synthesized by quantitative direct copolycondensation without catalysts at 200°C. The in vitro degradation, which was evaluated by measuring the weight loss of these copolymers in M/15 phosphate buffer solution (pH 7,2) without enzymes at 37°C, is strongly dependent on the kind and molecular weight of these copolymers, resulting in the formation of different degradation patterns such as parabola type (L -LA/DL -HBA system), linear type (L -LA/DL -LA system), and S type (L -LA/DL -HIVA and L -LA/DL -HICA systems).     

Successful treatment of blunt trauma involving complete laceration of the pancreas and duodenum in a 7-year-old child: Report of a case

The acute onset of peritoneal signs and shock in a 7year-old boy who had been hit in the epigastrium by a log-seesaw mandated surgical treatment. Enhanced computed tomography (CT) demonstrated complete laceration of the pancreas as well as duodenal injury, and a duodenoduodenostomy with distal pancreaticogastrostomy was subsequently performed. Temporary external drainage of the stomach and distal pancreas led to an uneventful recovery in the early postoperative period. Although the patient's postoperative development was appropriate for his age, the orifice of the distal pancreas spontaneously closed 2.5 years following surgery. We present this report to stress the fact that every effort should be made to preserve the pancreas following abdominal injury in children.     

Interaction of flufenamic acid on ethanol metabolism in rat.

Flufenamic acid (FA) is a widely used non-steroidal anti-inflammatory drug. It is also known to be an uncoupling agent of oxidative phosphorylation in mitochondria. The interaction of FA and ethanol has been of concern in the occupational health field, since alcohol consumption is a common habit among members of the working population. Thus, we investigated the effects of FA on ethanol metabolism in the rat. In the first experiment, FA and ethanol were administered intragastrically to male Wistar rats. Ethanol and acetaldehyde were measured in blood samples collected from the tail vein by head-space gas chromatography. In the second experiment, the interaction of FA and ethanol was observed in the perfused rat liver. The following items were monitored in perfused livers from both fed and fastd rats: uptake rate of ethanol, production rate of acetaldehyde, level of reduced pyridine nucleotides, and oxygen consumption rate. In the first experiment, the rats with FA showed significantly higher concentrations of both ethanol and acetaldehyde in blood after ethanol intake than the rats without FA. In the perfused liver, FA suppressed ethanol uptake, and increased acetaldehyde concentration in the effluent. FA decreased the level of intracellular reduced pyridine nucleotides which had been elevated by ethanol. FA caused an increase in the oxygen consumption rate, which was not altered by the coexistence of ethanol. It was concluded that FA suppressed ethanol metabolism due to suppression of acetaldehyde oxidation in the liver, despite its uncoupling effect on oxidative phosphorylation in mitochondria.     

Use of latissimus dorsi flap for reconstruction with prostheses after tumor resection

Five latissimus dorsi musculocutaneous flaps (LD flap) were used for reconstruction with prostheses after resection of tumors between 1984 and 1991 in our hospital. Bony structures were reconstructed with prostheses and in three cases autoclaved autobone grafts were also needed. The prostheses and adjacent grafts were then wrapped by the LD flaps. Tumor sites included one humerus, two thighs, and two knees. All but one case healed primarily. The sole case of infection was successfully treated with debridement and irrigation. Due to the LD flaps' plentiful blood supply, we believe infection of the prosthetics can be avoided and good clinical results can be achieved using the flap with autoclaved autograft prosthetic composite reconstruction. © 1994 Wiley-Liss, Inc.     

Late Effects of Childhood Acute Leukemia and Its Treatment

Late effects of childhood acute leukemia and its treatment were studied in 766 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.     

Serum thymidine kinase,a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase

We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase.