Seasonal changes in the circadian activity rhythm of light-dark (LD) and completely dark (DD) regimen in the mouse submandibular gland in the presence of light-dark (LD) and completely dark (DD) regimen

Influence of seasons on circadian activity changes and the influence of one and six weeks of DD upon these changes of acid phosphatase (AP) and beta-acetylglucosaminidase (AM) was studied in the submandibular gland of sexually mature male mice. Total enzyme activity was determined in tissue homogenates at four-hour intervals in March, June, October, and February under standard LD12/12 conditions and after one and six weeks of the DD regime. The rhythms were analysed according to cosinor method. Under constant lighting conditions the seasonal differences in the AM circadian activity rhythm were found. AP activity was considerably less influenced by seasonal changes. Both enzyme activity changes were independent of each other and each rhythm was differently influenced by DD. In the case of AM the most pronounced circadian activity changes had the highest amplitude and mesor occurred in summer. The strongest influence of DD upon this enzyme activity rhythm was observed in spring and summer especially after the first week, after six weeks the acrophase returned to the LD group value (spring). In autumn and winter the reaction to DD was different to that of summer and spring. For AP the circadian changes of activity were non-rhythmic in spring, whereas in all other seasons the acrophases occurred almost at the same time in the afternoon. In DD the activity rhythm significantly changed after six weeks. In all seasons, except spring the circadian rhythm of activity was not observed after six weeks of DD. An attempt was made to explain the observed results by the certain kind of genetic memory present in laboratory animals the neurohormonal system of which is influenced by seasonal changes.     

The survival and development of the shrimp Crangon crangon (L.), reared in the laboratory under non-circadian light-dark cycles

The shrimp, Crangon crangon (L.), has been reared from hatching to the late juvenile phase, under a circadian (LD 12 : 12) and two non-circadian (LD 8 : 8 and LD random) light-dark cycles. During the zoeal phase, survival in the non-circadian regimes was markedly lower than in the control circadian treatments. This effect supports the hypothesis that the entraining influence of daily environmental cycles is important in coordinating the various physiological processes within the animal. There was no evidence, however, that growth and morphological development were affected in the non-circadian regimes.     

The Notch pathway in prostate development and cancer

Abstract The Notch family of transmembrane receptors are important mediators of cell fate determination. Accordingly, Notch signaling is intimately involved in the development of numerous tissues. Recent findings have highlighted a critical role for Notch signaling in normal prostate development. Notch signaling is required for embryonic and postnatal prostatic growth and development, for proper cell lineage specification within the prostate, as well as for adult prostate maintenance and regeneration following castration and hormone replacement. Evidence for Notch as a regulator of prostate cancer development, progression, and metastasis has also emerged. This review summarizes our current understanding of the role of Notch pathway elements, including members of the Jagged, Delta-like, hairy/enhancer-of-split, and hairy/enhancer-of-split related with YRPW motif families, in prostate development and tumorigenesis. Data supporting Notch pathway elements as oncogenes and tumor suppressors in prostate tumors, as well as data implicating Notch receptors and ligands as potential markers of normal prostate stem/progenitor cells and prostate cancer stem/initiating cells, are also presented.     

Evaluation of a proposed breast cancer screening regimen.

The Forrest working group on breast cancer screening recommended routine mammography for women in the United Kingdom at ages 50, 53, 56, 59, 62, and 65. Benefits were costed at about 3000 pounds for each life year recovered, but there was no estimate of the cost of each life saved, and the consequent reduction in mortality from breast cancer in the general population of the United Kingdom was not estimated. The present study addressed both of these issues using an interactive computer modelling process. Long term savings were calculated at 900 deaths a year in England and Wales--that is, about 8% of the total deaths from breast cancer--and 9% of life years currently lost. The cost of each death saved from breast cancer was estimated at 39,000 pounds.     

The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients

The effect of selenium (Se) in reducing the toxicity of cisplatin in cancer patients was studied. Forty-one patients were randomized into group A (20 patients with Se administration in first cycle of chemotherapy as study cases and without Se in second cycle of chemotherapy as control) and group B (21 patients without Se in first cycle of chemotherapy and with Se in second cycle of chemotherapy). The 400 μg per day of Se as Seleno-Kappacarrageenan were administered from 4 before to 4 d after chemotherapy for study cases. The serum Se increased from 70.4±22.86 to 157.04±60.23 ng/mL (P<0.001) in patients received Se. The cisplatin dosage was iv administration in 60–80 mg/m² on the first day. The results showed that the peripheral WBC counts on day 14 after initiation of chemotherapy in study cases was significantly higher than the controls (3.35±2.01 vs 2.31±1.38 [×10⁹L])/L,p<0.05). On the other hand, the consumption of GCSF for the cases was significantly less than the controls (110.1±82.2 vs 723.6±192.6 IU,p<0.05). The volumes of blood transfusion for the study group were also significantly less than the controls (0 vs 62±38mL,p<0.05). The nephrotoxicity of cisplatin was measured by urine enzymes (NAG, GGT, AAP, LAP, and ALP) were determined prior to and at 2, 24, 48, and 72h after initiation of chemotherapy. The urine enzymes NAG, GGT, AAP, and ALP after chemotherapy for cases were significantly lower than the controls. No toxicity of Seleno-Kappacarrageenan was noted. The above results suggest that the Se can be used as an agent for reducing the nephrotoxicity and bone marrow suppression induced by cisplatin.     

Prevention of prostate cancer through custom tailoring of chemopreventive regimen

One practical way to control cancer is through chemoprevention, which refers to the administration of synthetic or naturally occurring agents to block, reverse or delay the process of carcinogenesis. For a variety of reasons, the most important of which is human acceptance, for chemopreventive intervention naturally occurring diet-based agents are preferred over synthetic agents. For a long time, the prevailing mantra of cancer chemoprevention has been: "Find effective agents with acceptable or no toxicity and use them in preventing cancer in relatively healthy people or individuals at high risk for developing cancer". In pursuing this goal many naturally occurring phytochemicals capable of affording protection against carcinogenesis in preclinical settings in experimental animals have been described. However, clinical trials of single agents have yielded disappointing results. Since carcinogenesis is a multistage phenomenon in which many normal cellular pathways become aberrant, it is unlikely that one agent could prove effective in preventing cancer. This review underscores the need to build an armamentarium of naturally occurring chemopreventive substances that could prevent or slow down the development and progression of prostate cancer. Thus, the new effective approach for cancer prevention "building a customized mechanism-based chemoprevention cocktail of naturally occurring substances" is advocated.     

Effect of an exercise regimen on development of hypertension in rats

The possibility that a forced exercise regimen might prevent the development of hypertension induced in rats both by renal encapsulation and chronic administration of deoxycorticosterone acetate (DOCA) and NaCl has been studied. In renal hypertensive rats, forced exercise at 0.4 to 1.25 miles/day, 7 days/wk for 16-22 wk failed to prevent the development of hypertension and cardiomegaly and reduced renal concentrating ability accompanying the hypertension. In DOCA-treated rats (10 mg/wk), forced exercise at 0.4 and 0.8 mile/day, 7 days/wk for 16 wk also failed to prevent both the development of hypertension and cardiomegaly. A review of data of others reveals that exercise may delay the development of hypertension in both Dahl salt-sensitive and spontaneously hypertensive (SHR) rats and may modestly reduce the maximal level of pressure attained. Of the four models of hypertension studied to date in rats, the Dahl salt-sensitive strain appears to be the one that responded best to exercise, although blood pressure eventually reached that of sedentary controls.     

The effect of light-dark adaptation on the ultrastructure ofLimulus lateral eye retinular cells

Summary The fine structure of retinular cells within lateral eyes ofLimulus polyphemus which had been dark or light adapted for 12 h in vivo was studied via electron microscopy. The ommatidium to ommatidium and retinular cell to retinular cell variability observed in light microscope studies was confirmed. The rhabdomeric microvilli were longer and narrower, the area of contiguous microvillar membranes greater, the endoplasmic reticulum less abundant and the mitochondrial granules (? calcium containing) more numerous in well dark adapted than in well light adapted retinular cells (Figs. 1, 3, 4, 7, 8) and membrane whorls or vacuoles were present in the peripheral cytoplasm of very well light adapted retinular cells (Fig. 6). Phagocytotic vesicles, multivesicular bodies and lysosomes were present in the interrhabdomeral cytoplasm of partially light adapted retinular cells (Figs. 1, 2, 3, 10). The number of retinular cell microvilli in contact with the eccentric cell dendrite was smaller in very well light adapted than in well dark adapted ommatidia (Fig. 9). The possible functional significance of these light-dependent structural changes is discussed.This investigation was supported in part by Grant 2 RO1 EY 00236 National Eye Institute, National Institutes of HealthMember of the SFB 160 of the Deutsche Forschungsgemeinschaft     

Serotonin synthesis and its light-dark variation in the rat retina

Retinal circadian rhythms are driven by an intrinsic oscillator, using chemical signals such as melatonin, secreted by photoreceptor cells. The purpose of the present work was to identify the origin of serotonin, the precursor of melatonin, in the retina of adult rat, where no immunoreactivity for serotonin or tryptophan hydroxylase had ever been detected. To demonstrate local synthesis of serotonin in the rat retina, substrates of tryptophan hydroxylase, the first limiting enzyme in the serotonin pathway, have been used. Tryptophan, in the presence of an inhibitor of aromatic amino acid decarboxylase, enhanced 5-hydroxytryptophan levels, whereas alpha-methyltryptophan, a competitive substrate inhibitor, was hydroxylated into alpha-methyl-5-hydroxytryptophan. Tryptophan hydroxylase substrate concentration was higher in the dark period than in the light period, and formation of hydroxylated compounds was increased. The presence of tryptophan hydroxylase mRNA in the rat retina was confirmed by RT-PCR. Taken together, the results support the local synthesis of serotonin by tryptophan hydroxylation, this metabolic pathway being required more critically when 5-HT is used for melatonin synthesis.