Adsorption of Human Recombinant Erythropoietin on Dialysis Membranes In Vitro

Abstract: The adsorptive characteristics of 5 dialysis membranes for recombinant human erythropoietin (EPO) were studied in vitro in a closed circuit system. For 120 min, EPO added with bovine serum was significantly adsorbed by polymethylmetacrylate (PMMA) and polyacry–lonitrile (PAN) membranes but not by Cuprophan, ethylene vinyl alcohol (EVAL), or polysulfone (PS) membranes. In addition the EPO adsorptive rate, as well as that of β₂–microglobulin (β₂–MG), was greater with a PMMA membrane than with a PAN membrane. EPO was not detected in the ultrafiltrate at 15 min with 5 membranes. These results indicate that EPO was eliminated by membrane adsorption only with some dialysis membranes.     

Stereoselectivity of a potent calcium antagonist, 1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism.     

Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

Intense immunoreactivity for Mn-superoxide dismutase (Mn-SOD) in cholinergic and non-cholinergic neurons in the rat basal forebrain

The immunohistochemical localization of manganese (Mn)-superoxide dismutase (Mn-SOD) was studied in the rat basal forebrain using polyclonal antibodies to Mn-SOD. Neurons of the basal forebrain exhibit a high density of Mn-SOD immunoreactivity. Double immunostaining with a monoclonal antibody to choline acetyltransferase demonstrated that both cholinergic and non-cholinergic neurons in the basal forebrain are intensely immunoreactive for Mn-SOD.     

Clinical effects of oxybutynin hydrochloride (Pollakis)--especially in the treatment of pollakisuria, urgency and urinary incontinence

The effects and the safety of oxybutynin hydrochloride were investigated in 52 patients, 17 male and 35 female, with the chief complaints of pollakisuria, urgency and urinary incontinence. Clinical responses to the drug were assessed mainly by the subjective symptoms of the patients. The diagnoses of these patients were neurogenic bladder in 17, unstable bladder in 16 and others in 19 patients. The average administration period was 66.8 days. The rate of global improvement (excellent and good) was 55% in the 2 mg dose given 3 times daily group, 68.2% in the 3 mg dose given 3 times daily group. Side effects, such as dry mouth, were observed in 2 of the 52 patients (3.8%), but no serious side effects were observed. The rate of global utility (remarkable and moderate) was 67.3%. These data indicate that oxybutynin hydrochloride seems to be useful and safe for the treatment of pollakisuria, urgency and urinary incontinence.     

A case of polycythemia vera complicated by chronic renal failure under hemodialysis requiring parathyroidectomy for secondary hyperparathyroidisim

A case of polycythemia vera complicated by chronic renal failure under maintenance hemodialysis requiring parathyroidectory (PTH) for secondary hyperparathyroidism (2° HPT) is reported. A 62 year old female presented with 75000 white blood cells (WBC)/μl, 703×10⁴ red blood cells (RBC)/μl, 23×10⁴ platelets (PLT)/μl, hyperuricemia and hypertension in 1970 and the diagnosis of polycythemia vera was made. Hemodialysis was started in October 1974 for chronic renal failure. Blood cells in peripheral blood rapidly decreased in number after the beginning of dialysis, reaching the level of 10000∼20000 WBC/μl, and 150∼250×10⁴RBC/μl. In August 1988, marked bone resorption in X-ray picture and high serum alkaline phosphatase and parathyroid hormone (PTH) noted along with 17400 WBC/μl, 370×10⁴RBC/μl and 35.9×10⁴PLT/μl. After subtotal PTX removing 3.21g parathyroid gland, serum PTH rapidly fell. At 3 months after PTX, WBC rose to 23600/μl, RBC 372×10⁴/μl and PLT 94.0×10⁴/μl. At 6 months, WBC was to 31000/μl, RBC 429×10⁴/μl and PLT 78.0×10⁴/μl, suggesting an inhibitory action of PTH on not only RBC, but also WBC and PLT.     

Kinetic study of glomerular epithelial cells associated with segmental glomerular sclerotic lesions with adhesion in spontaneously diabetic WBN/Kob rats

Background We previously found that glomerular epithelial cells play an important role in the formation of adhesive lesions. Glomerular sclerotic lesions develop after the inital adhesive lesions. Methods Two series of experiments were done with spontaneously diabetic WBN/Kob rats. These rats develop segmental glomerular sclerotic lesions with aging. The first series of experiments was intended to clarify the kinetics of glomerular cells on progressive glomerular damage in these rats. The second series of experiments was designed to study the relationship between proliferation (judged by % bromodeoxyuridine-positive cells) of glomerlar epithelial cells and sclerotic lesions with adhesions. Results In the first series, rats having increased proteinuria showed segmental glomerular sclerotic lesions with adhesions. At the same time, increased labeling indices of tuft cells and epithelial cells of Bowman's capsule were observed. In the second series, no significant increase in the labeling indices of tuft cells with sclerotic lesions was observed, compared to tuft cells without sclerotic lesions. In sclerotic lesions with adhesion, bromodeoxyurdine-positive cells were observed that were not distinguishable as podocytes or epithelial cells of Bowman's capsule. The highest labelling index was noted in the epithelial cells of Bowman's capsules with sclerosis. Conclusion This study shows that the proliferation of glomerular epithelial cells (mainly epithelial cells of Bowman's capsule) occurs in glomerular sclerotic lesions with adhesions.     

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.