Mild hypothermia promotes pro-inflammatory cytokine production in monocytes

Hypothermia is often associated with compromised host defenses and infection. Deteriorations of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. We have previously shown that mild hypothermia modifies cytokine production by peripheral blood mononuclear cells. In this study, the effects of hypothermia on the monocytic production of several cytokines and nitric oxide (NO) were determined. Monocytes obtained from 10 healthy humans were cultured with lipopolysaccharide (LPS) under hypothermic (33 degrees C) or normothermic (37 degrees C) conditions for 48 hours. We performed flow cytometric analysis for simultaneous measurement of interleukin (IL)-8, IL-1beta, IL-6, IL-10, IL-12p70, and tumor necrosis factor (TNF)-alpha in culture supernatants. NO production was quantified as accumulation of nitrite in the medium by a colorimetric assay. Compared with normothermia, mild hypothermia raised the levels of IL-1beta, IL-6, IL-12p70, and TNF-alpha produced by monocytes stimulated with LPS. On calculating the ratios of these elevated cytokines to IL-10, however, only IL-12p70/IL-10 and TNF-alpha/IL-10 ratios were significantly elevated under hypothermic conditions. In contrast, hypothermia did not affect NO production. This study demonstrates that mild hypothermia affects the balance of cytokines produced by monocytes, leading to a pro-inflammatory state. Specifically, monocytic IL-12 and TNF-alpha appear to be involved in the immune alterations observed in mild hypothermia. However, the clinical significance of these phenomena remains to be clarified.     

Allelotyping analysis at chromosome 13q of high-grade prostatic intraepithelial neoplasia and clinically insignificant and significant prostate cancers

BACKGROUND: Loss of heterozygosity (LOH) at 13q is one of the most common chromosomal alterations in high-stage prostate cancer, yet little is known about genetic changes in earlier-stage prostate cancer. METHODS: We used five microsatellite markers at 13q14, 21, and 33 to compare LOH frequencies in 51 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 21 cases of incidental prostate cancers (IPCs), 31 cases of latent prostate cancers (LPCs), and 102 cases of clinical prostate cancers (CPCs). RESULTS: The frequency of LOH at 13q with at least 1 marker was 0%, 38%, 56%, and 49% in HGPIN, IPCs, LPCs, and CPCs, respectively. No statistically significant difference was found between the types of prostate cancer. Allelic loss at 13q14 was significantly more frequent in pT4 tumors than in earlier-stage tumors (P=0.011). CONCLUSIONS: Allelic loss at 13q is not only an important event in the metastasis of prostate cancer, but also associated with the initiation of the tumor.     

Usefulness of an immunochromatographical assay, PSA Rapid Test as a primary screening test for prostate cancer

Background The recent rapid increase of mass screening for prostate cancer by measuring PSA in Japan will increase the economic burden to the healthcare system. PSA Rapid Test (PRT) is a simple inexpensive test. The usefulness of PRT as a primary screening test for prostate cancer was evaluated. Methods When we conducted educational lectures for prostate cancer in our city, screening for prostate cancer using PRT was offered to the male participants. The results of the tests were handed to participants in writing at the end of the lectures. When the results were judged as positive, letters of referral to our institute were enclosed. Results One hundred and fourteen (18.6%) of 614 men were judged as positive by PRT. Of the 114 men with positive PRT, 73 (64%) visited our institution. Finally, 37 men underwent a transrectal prostate biopsy and a diagnosis of prostate cancer was made in 21 men (3.4% of all participants). The total costs for the PSA tests in this study were summed to be approximately $2,300, while they would be approximately $9,200 if all participants had undergone screening using the conventional quantitative method from the outset. Conclusion PRT is a low-cost method to detect patients with prostate cancer. We believe the PRT is useful as an initial screening test for detecting prostate cancer and that the combination of the PRT and more precise quantitative testing would be a reasonable way to reduce the cost and achieve high detection rate.     

Intermittent androgen deprivation therapy may prolong the duration of androgen dependence of well-differentiated prostate cancer

We previously reported the results of a pilot study of intermittent androgen deprivation (IAD) therapy in which surveillance was performed when PSA level fell below 0.3 ng/ml and androgen deprivation was resumed when PSA level exceeded 2.0 ng/ml. In the present study, we compared the duration of androgen dependence in patients treated with IAD with that in patients with continuous androgen deprivation (CAD) therapy. Forty-six patients with clinically localized or metastatic prostate cancer, or biochemical recurrence after radical prostatectomy were treated with IAD from 1995 to 2003. Patients in or after the second cycle of IAD (30 patients) were evaluated for duration of androgen dependence. Patients whose serum PSA nadir became <0.3 ng/ml (33 patients) represented a control group of CAD. The overall 5-year biochemical progression-free rate was 58% and 89% in the IAD and CAD groups, respectively; there was no significant difference between the two groups (p=0.5). Subgroup analysis showed that, irrespective of metastasis, the 5-year biochemical progression-free survival rate in the IAD group was not significantly different from that in the CAD group. However, IAD offered significantly better results for well-differentiated prostate cancer, whereas CAD offered significantly better results for moderately or poorly differentiated prostate cancer. The results obtained from this retrospective and nonrandomized study suggested that IAD may be a feasible treatment for well-differentiated prostate cancer.     

Pressor action of propranolol; with special reference to relationship between the pressor action and peripheral vascular tone]

We showed in previous studies that pro pranolol produced a pressor action in the rat, and that this action was also observed in the spinal rat infused with adrenaline, noradrenaline and a mixture of isoproterenol and vasopressin, but not with vasopression alone. The action was also observed in the guinea pig infused with adrenergic beta-stimulants. In the present work, conditions in the peripheral vessels in which propranolol observed in the spinal rat infused with a mixture of various doses of isoproterenol and vasopressin. The effect of propranolol on the blood pressure in guinea pigs and rabbits with a reduced vasoconstrictive tone in the peripheral vascular beds with alpha-blockade was studied. Propranolol produced a pressor action in the spinal rat infused with a mixture of isoproterenol and vasopressin, and the magnitude of the rise depended on the mixing rate of the doses of these two drugs. The drug also produced a sustained rise in blood pressure in guinea pigs and rabbits treated with alpha-blockers. Thus, it is concluded that propranolol produces a marked pressor action when peripheral vessels are maintained in conditions with an appropriate constrictive and beta-adrenoceptive vasodilator tone.