Urinary nitrite excretion in low birth weight neonates with systemic inflammatory response syndrome.

Increased nitric oxide (NO) levels are thought to play an important role in the pathophysiology of the systemic inflammatory response syndrome (SIRS) which is caused by disseminated vascular endothelial damage. Clinical studies have shown that urinary nitrite (NO2-) and nitrate (NO3-) excretions can be utilized as indexes of NO formation. The SIRS and NO relationship was investigated in 15 neonates with SIRS, gestational age 32.5 +/- 4.4 weeks and weight 1,737 +/- 753 g. The control group comprised 18 neonates with a gestational age of 32.8 +/- 3.5 weeks and a weight of 1,778 +/- 538 g. There was no significant difference in birth weights and gestational ages between the two groups (p > 0.05 and p > 0.05). The urinary nitrite levels obtained in the subjects were normalized for urinary creatinine concentrations. The mean urinary nitrite levels in the control group neonates were found to be 4.22 +/- 1.8 micromol/mmol creatinine on the 1st day, 4.09 +/- 2.28 on the 2nd, 3.62 +/- 1.6 on the 3rd, and 4.01 +/- 1.12 micromol/mmol creatinine on the 7th day. There were no statistically significant differences between these levels (p > 0.05). We determined urinary levels of nitrite in neonates in the study group within the first 24 h of SIRS symptoms and found these levels (18.35 +/- 11.16 micromol nitrite/mmol creatinine) to be elevated as compared with those of the control subjects on the 7th day of life (p < 0.0005). In conclusion, urinary nitrite excretion is significantly elevated in neonates with SIRS due to septic events, and these results suggest that NO might play a part in SIRS.

Influence of exercise training and age on uncoupling protein mRNA expression in brown adipose tissue.

The ability to regulate body temperature diminishes with age. Exercise training is known to increase cardiovascular performance, and there is some evidence of a cross-adaptation between exercise and cold tolerance in young rats. The present study was designed to examine the effects of physical training by treadmill running on the capacity for brown adipose tissue (BAT) thermogenesis in young and old rats. To this end, we assessed BAT uncoupling protein (UCP) mRNA expression in sedentary and exercise-trained 5- and 25-mo-old F-344 rats. The amount of UCP mRNA, whether expressed as per unit RNA or per BAT, did not change with either age or training. These data indicate that there is no cross-adaptation by exercise on adaptive thermogenesis in BAT in either young or old rats.

Nuclear casein kinase 2 (CK-2) activity in human normal, benign hyperplastic, and cancerous prostate.

In previous work, we had observed that chromatin-associated nonhistone protein phosphorylation, catalyzed by intrinsic protein kinase reaction in chromatin preparations from human benign prostatic hyperplasia (BPH) prostate samples was markedly elevated, compared with the normal prostate chromatin samples [Rayan et al: Cancer Res 45:2277-2282, 1985]. The properties of this protein kinase reaction were suggestive of the involvement of casein kinase(s). By employing the specific synthetic substrate for casein kinase 2 (CK-2) for assays in cellular fractions, we have shown that this protein kinase is present in human prostate chromatin. Its activity is increased in BPH chromatin by about 25-fold, as compared with its activity in the normal prostate chromatin. This suggests that CK-2 is a possible mediator of the enhanced phosphorylation of chromosomal proteins in BPH chromatin. By comparison, CK-2 activity in chromatin preparations from prostatic carcinoma samples was markedly less elevated than that of the BPH chromatin. Immunohistochemical analysis of the enzyme in human frozen sections of prostate tissue samples showed that the enzyme immunostaining was diffuse in the cytoplasm, but more intense in the nucleus, especially in the nucleoli. In general, the staining corresponded with the enzymic data. However, sections from prostatic carcinoma samples appeared to show differential staining, depending on the Gleason's grade of the sample. The samples with higher Gleason's grade showed less intense immunostain in the nucleus, compared with samples of lower Gleason's grade. Further, regions of sections in samples with higher Gleason's grade did not show any immunostaining. These differences in the characteristics of CK-2 expression in prostatic carcinoma samples may be potentially significant, but need to be evaluated further for their significance to the pathobiology of prostatic neoplasia.

Association of casein kinase 2 with nuclear chromatin in relation to androgenic regulation of rat prostate.

Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in growth control. We have studied the activity and subcellular location of CK-2 in adult rat ventral prostate in relation to androgen withdrawal and administration. Androgen deprivation by castration results in a faster decline in CK-2 activity associated with prostatic nuclei than that in the cytosol. Nuclear CK-2 associated with chromatin is reduced at an even greater rate than that in the total nucleus. Reversal of these events by administration of a single dose of 5 alpha-dihydrotestosterone to adult rats castrated 144 hr previously was accompanied by a differential early enhancement of chromatin-associated CK-2 activity, with a concomitant decrease in the CK-2 activity present in the cytosol. Changes in the nuclear CK-2 activity correlated with the immunostainable enzyme protein in the nucleus. We propose that androgens evoke translocation of CK-2 from the cytoplasm to the nucleus (nucleoplasm) where its enhanced association with the chromatin constituents takes place. Conversely, withdrawal of circulating androgens due to castration evokes a dissociation of CK-2 from chromatin and eventual translocation of nucleoplasmic CK-2 to the cytoplasm. Modulations in the association of CK-2 with nuclear chromatin may represent an important mechanism of post-transcriptional regulation of nuclear CK-2 in relation to androgen action in the prostate.