Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effects of salt intake on serum lipoprotein and apolipoprotein metabolism

Recently, food intake in Japan has been characterized by an increase in fat intake, especially animal-fat intake and the maintenance of excess salt (sodium chloride) intake. It is generally accepted that the increase in fat intake is closely related to atherosclerosis, and excess salt intake is a high risk factor for the development of hypertension and cerebrovascular lesions. So far, in almost all reports, the increase in fat intake and excess salt intake have been studied independently, and there have been few reports on the combined effects of these two factors. Taking the above things into consideration, it would seem to be very interesting to investigate the effect of excess salt intake on lipid metabolism. In this paper, we studied the effects of excess salt intake on lipoprotein and apolipoprotein metabolisms, using stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Kyo: Wistar rats (WKY) as model animals. The results obtained were as follows: A significant increase in the concentration of serum total cholesterol (TC) was observed in SHRSP and WKY, when the rats were given a regular diet (CE-2, Clea Japan Inc.) and 1% sodium chloride solution (1% NaCl) as drinking water for 4 weeks. This was accompanied by a tendency toward increases in the concentrations of serum apolipoproteins in both strains. These results suggest that excess salt intake could accelerate the production of serum total lipoproteins in SHRSP and WKY, when the rats are fed a regular diet. Next, 1% NaCl and a high-fat and high-cholesterol diet (HFC diet) were simultaneously given to SHRSP and WKY for 6 weeks. The effects of simultaneous administration on lipoprotein and apolipoprotein metabolisms were compared with those of HFC feeding. One percent NaCl did not markedly affect hypercholesterolemia in WKY, while it induced more marked hypercholesterolemia in SHRSP that was associated with extreme elevations of serum TC and the atherogenic index (A.I.). This deleterious effect of 1% NaCl in SHRSP was due to drastic elevations of cholesterol contents in the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fractions. This was also associated with marked increases in apo B contents in the VLDL, IDL and LDL fractions and significant increases in apo E contents in the VLDL and IDL fractions. These results indicate that 1% NaCl induced much larger increases in serum atherogenic beta-lipoproteins in SHRSP.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acquired cystic disease of the kidney and renal carcinoma in haemodialysis patients: ultrasonographic evaluation.

Ultrasonography was performed in 661 dialysis patients and acquired cystic disease of the kidney was found in 156 (125 men and 31 women). A higher incidence of cystic disease was found in males. There was no significant difference between the patients with and those without acquired cystic disease in terms of average age, but the duration of haemodialysis in those with acquired cystic disease was significantly longer. There was an increased incidence of cystic disease in patients with glomerulonephritis and the duration of haemodialysis in these patients was significantly longer. This suggests that the increased incidence of acquired cystic disease of the kidneys in the patients with glomerulonephritis is simply related to the longer duration of treatment. Twelve patients with renal carcinoma were found in this study. The average age at diagnosis of renal carcinoma was not significantly different between the patients with and those without acquired cystic disease, but the duration of dialysis was significantly longer in renal carcinoma patients with acquired cystic disease. The incidence of renal carcinoma in dialysis patients with acquired cystic disease was 3.85% and in those without it was 1.19%. These rates are considerably higher than those found in the general population and indicate that the risk of renal carcinoma is higher in dialysis patients both with and without acquired cystic disease.     

Effect of high-dose medroxyprogesterone acetate on plasma hormone levels and pain relief in patients with advanced prostatic cancer.

High-dose medroxyprogesterone acetate (MPA) was given orally to 7 patients with advanced prostatic cancer and severe pain due to bone metastases; 5 patients had stable and 2 had progressive disease. Pain relief was obtained in 6 patients. Two patients who reported complete relief of pain showed suppressed levels of gonadotrophins after MPA treatment. In the other patients, suppression of plasma gonadotrophin levels was observed before treatment. The plasma levels of prolactin, growth hormone and thyroid stimulating hormone were not affected by MPA. Only 1 patient showed suppression of plasma adrenocortical trophic hormone. The plasma levels of cortisol and dihydroepiandrosterone sulphate were suppressed in 6 patients, but there was no correlation between the suppression and the occurrence of pain relief. These findings suggest that the mechanism of pain relief by high-dose MPA may be very complicated.     

Pemphigus Vulgaris Associated with Autoimmune Hemolytic Anemia and Elevated TNFα

A 76-year-old female was admitted with many bullae and erythema on her trunk and extremities. A biopsy specimen showed significant intercellular edema in the lower epidermis and eosinophilic infiltration into the dermis and the epidermis. Immunofluorescent staining revealed the deposition of IgG in the intercellular area of her prickle cells. From these histologic findings and the typical clinical features, we diagnosed her as having pemphigus vulgaris. Examination of her blood revealed that she also suffered from autoimmune hemolytic anemia. Despite intensive treatment with prednisolone, she finally died. This case is of interest because of its rarity and the TNFα detected significantly in the blister fluid of this patient.     

Chemo-endocrine therapy in patients with stage D2 prostate cancer

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.     

A case of chronic persistent cough (CPC) caused by gastroesophageal reflux (GER) (including a study of CPC caused by suspected GER)]

A patient, an 80-year-old female, had complained of a cough for 20 weeks, and was not cured by cough medicine. Gastroesophageal reflux was considered as the cause of the cough because of her symptoms and gastrointestinal fiberscopy (GIF) and barium meal studies. She made favorable progress on a histamine H2 blocker and cysapurid for 4 weeks. Therefore we diagnosed her cough as caused by gastroesophageal reflux. We also studied the incidence of chronic persistent cough in patients suspected of gastroesophageal reflux because of symptoms and GIF results. Among 676 cases examined by GIF at Niigata-kenritsu Myoko Hospital, we detected 7 cases who complained of heartburn and in whom we observed hiatal hernia and reflux esophagitis by GIF. Only one of them, the present case, complained of a cough. CPC caused by gastroesophageal reflux is not seen frequently, but the possibility of GER as the cause of CPC should be considered.     

Malacoplakia of the bladder: Efficacy of enoxacine therapy

Malacoplakia of the urinary bladder was seen in a 69-year-old woman with haematuria. We firstly treated her with distigmine bromide, ascorbic acid and trimethroprim-sulfamethoxazole. Haematuria subsided but the lesion did not change after 6 weeks. Thereafter we tried enoxacine therapy. Eight weeks after the medication the tumorous leson disappeared. Bladder biopsy performed 4 months after the initiation of the treatment revealed predominantly granulation tissue. We can find no previous case treated successfully with long-term enoxacine.     

Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production

The effects of prostaglandin E₂ (PGE₂) on cytokine productionand proliferation of the CD4⁺ human helper T cell clone SP-B21were investigated. In cells stimulated with antl-CD3 mAb, PGE₂inhibited cell proliferation and the production of all the cytokinesexamined. Addition of rlL-2 fully restored the prollferatlveresponse and partially restored the production of IL-4 and IL-5,but not that of other cytokines. In contrast, In cells stimulatedwith phorbol myrlstate acetate (PMA)/A23187, PGE₂ enhanced theproduction of IL-4 and IL-5, and only partially inhibited theproduction of other cytokines. Therefore, the effects of PGE₂vary depending on the mode of T cell activation, and the IL-4and IL-5 are regulated differently from other cytokines. Ina mobility shift assay, only the NF-B (p50/p5O) homodlmer wasobserved in a complex formed with the B sequence in unstlmulatedSP-B21 cells. When cells were stimulated with antl-CD3 mAb orPMA/A23187, a complex formation of NF-B (p50/p65) heterodlmerwith the B sequence was induced. Interestingly, PGE₂ or di-butyryl(Bt₂cAMP abolished the binding of NF-B (p50/p65) heterodlmerto the B sequence in cells stimulated with antl-CD3 mAb butnot with PMA/A23187. Our results suggest that the target ofPGE₂ action is a component in the signal transductlon pathwayleading to the activation of protein klnase C. However, theinhibition of the T cell activation signals by PGE₂ is selective.PGE₂ enhanced the complex formation with NF-AT, AP-1 and CLEOsequences when the cells were activated by either anti-CD3 mAbor PMA/A23187 stimulation. It seems therefore that PGE₂, byelevating cAMP levels, interferes with the activation pathwayfor NF-B but not for NF-AT, AP-1 or CLEO binding protein.