Temporal Aspects of the Pathophysiology of Human Ulcer Disease

In this paper, a peptic ulcer is considered from the perspective that it is representative of a heterogeneous group of multifactorial determined or influenced disorders having a common pathomorphologic expression. This heterogeneity involves several pathophysiological attributes, including both functional (including secretory and motility events and their respective driving mechanisms) and morphologic alterations that relate to mucosal resistance. Patients with duodenal ulcer (DU) have been observed to exhibit alterations, in comparison to normal subjects, in the circadian rhythm characteristics of several gastrointestinal functions. Prominent among these are altered amplitudes of several circadian-organized gastric variables, such as intragastric pH, gastrin, pepsinogen and gastric mitotic index. With respect to any given variable, a reduced group amplitude (a measure of one-half the peak-trough difference of a 24-hr rhythm) could signify an increased dispersion of acrophases (the location of the peak of a circadian rhythm along the 24-hr time scale) reflecting interindividual variation in synchronization schedules, sleep-wake patterns, or chronobiologic alterations. A reduced interindividual amplitude further supports the concept of the heterogeneity of peptic disease. A decrease in the intraindividual amplitude of certain gastric rhythms implies an altered temporal pattern over the 24 hr. This is consistent with the hypothesis of a decrease in the amount of time available for recovery of a given function or set of integrated functions, and hence, increased susceptibility to mucosal injury. Normal high-amplitude variation in gastrointestinal functioning over the 24 hr appears to be required for natural restoration of the gut.     

Circadian Rhythm of Gastric Acid Secretion in Active Duodenal Ulcer: Chronobiological Statistical Characteristics and Comparison of Acid Secretory and Plasma Gastrin Patterns with Healthy Subjects and Post-Vagotomy and Pyloroplasty Patients

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p < 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p=0.034) circadian rhythm in unstimulated acid secretion in a group (N=14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N=17) of post-vagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.     

小儿消化性疾病的胃电图变化及与临床特点和胃镜特征的关联性

目的:分析小儿消化性疾病的胃电图变化及与临床病理特征和胃镜特征的关联性。方法:选取2018年1月至2019年5月我院儿科收治的经胃镜和病理学两种方式诊断为消化性疾病的患儿54例为观察组,另选取无胃肠道疾病的健康儿童40例为对照组。比较两组胃电图参数(频率均值和波幅均值),54例胃电图诊断后纤维胃镜检查结果,分析消化性疾病患儿HP感染与临床病理特征、溃疡面积的关系。结果:各组胃病患者胃电慢波频率均值各不相同(P0.05),三组患者胃电慢波波幅均值相比差异具有统计学意义(P0.05);且浅表性胃炎组、胆汁反流性胃炎组患者胃电慢波频率均值、胃电慢波波幅均显著低于胃溃疡组(P0.05);浅表性胃炎组患者胃电慢波频率均值显著低于胆汁反流性胃炎组(P0.05)。胆汁反流性胃炎组患者胃电慢波波幅显著低于浅表性胃炎组(P0.05)。胃镜检查结果显示,其中浅表性胃炎的诊断符合率较高,达90.00%,胃溃疡符合率为60.71%,胆汁反流性胃炎符合率为83.33%。HP检测结果显示,HP阳性患儿占总例数的77.78%(42/54),HP阴性患儿占总例数的22.22%(12/54);HP阳性组患儿淋巴滤泡形成、胃黏膜萎缩、胃黏膜炎性活动的发生率明显高于HP阴性组,差异具有统计学意义(P0.01);HP阳性组溃疡范围2 cm的患儿比例明显高于HP阴性患儿,差异具有统计学意义(P0.01)。结论:小儿消化性疾病胃电图存在餐后NSWP的下降及节律过缓的上升,胃电图检查和胃镜检查在诊断上有较高的符合率,HP感染科引起胃黏膜组织学改变,可作为小儿消化性疾病的靶向治疗。     

Circadian rhythm of gastric acid secretion in active duodenal ulcer: chronobiological statistical characteristics and comparison of acid secretory and plasma gastrin patterns with healthy subjects and postvagotomy and pyloroplasty patients

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p less than 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p = 0.034) circadian rhythm in unstimulated acid secretion in a group (N = 14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N = 17) of postvagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.     

Genetic and evolutionary implications in peptic ulcer disease

The evidence for a genetic component in peptic ulcer disease has been based on twin, family, and blood group studies. A polygenic model for the inheritance of peptic ulcers has been displaced by a genetic heterogeneity model based on several lines of evidence, some of the most powerful being recent work using subclinical markers. One marker in particular, an elevated level of serum pepsinogen I (PG I), a pepsin precursor produced by the gastric mucosa, secreted into the stomach lumen and also appearing in the bloodstream, has been found to be associated with a subgroup of duodenal ulcer patients. Segregation analysis of elevated serum PG I in duodenal ulcer sibships demonstrates familial aggregation consistent with autosomal dominant inheritance. Elevated PG I is also accompanied by gastric hyperacidity and presumably indicates those individuals with an increased mass of chief and parietal cells, and thus an increased capacity for peptic activity, an important element in the pathogenesis of ulcer disease. An evolutionary hypothesis based on selection for peptic activity and acidity is offered to explain several of the epidemiologic and genetic elements of this group of chronic diseases.     

Rhythmic Patterns in Incidence of Peptic Ulcer Perforation Over 5.5 Decades in Norway

The incidence of ulcer perforation in 1480 patients treated in the Bergen area of Norway between 1935 and 1990 was analyzed for daily (circa-dian), weekly (circaseptan), and yearly (circannual) time effects. A circadian rhythm was found overall that was reproducible and fairly stable across seasons, decades, and days of the week. After subgrouping, a circadian rhythm was found in younger patients, males, and duodenal perforations, while a 12h (circasemidian) rhythm characterized ulcer perforation for women and for gastric ulcers. Duodenal perforations showed highest incidence in the afternoon, while gastric perforations showed a major peak around noon and a secondary peak near midnight. For duodenal ulcer perforation, the circannual pattern was characterized by a 6-month rhythm, with significantly higher incidence in May-June-July and in November-December in most subgroups. A circaseptan rhythm was not found, but there was a significantly higher incidence on Thursday-Friday as compared to Sunday-Monday. The pathophysiological mechanisms underlying the perforation of an ulcer thus seemed to show pronounced circadian and 6-month rhythmic variations, much less so circaseptan or circannual rhythms. While it is likely that exogenous environmental and/or societal factors play a significant role, variations in ulcer perforation may be related to endogenous biological rhythms in pathophysiological factors since the circadian pattern of duodenal perforations follows that for gastric acidity. Knowledge of the temporal patterns in peptic ulcer perforation and associated pathophysiologic factors should prove useful in optimizing the chronotherapeutic management of ulcer disease.     

消化性溃疡与幽门螺杆菌关系的内窥镜探查

目的:探讨幽门螺杆菌(Hp)与消化性溃疡(PU)的关系。方法:检测167例PU患者Hp阳性率,使用胃镜观察溃疡形态、大小和部位。结果:167例PU患者Hp阳性检出率为87.43%,胃溃直径大于1.5 cm者与,胃溃直径小于0.5cm,溃疡处于活动期者与愈合期和瘢痕期者,Hp阳性检出率有显著差异(P<0.05)。结论:Hp感染与溃疡的发生有密切关系,溃疡患者病情越重,Hp感染程度越高,但Hp阳性溃疡并不加重消化道出血现象发生。     

Circadian Rhythm and Seasonal Variations in Basal cAMP Content of Rat Heart Ventricles

The cAMP content in rat heart ventricles was studied at 3-hr intervals during 24hr at different times of the year. A significant circadian rhythm in cAMP content was found. Time of the year reproducibly influenced the 24-hr mean, the amplitude as well as the peak value in cAMP in relation to circadian time.     

Circadian rhythm of thymosin-alpha 1 in normal and thymectomized mice

Studies by many investigators have demonstrated that the immune system is subject to regular circadian fluctuation. Some rhythms that have been reported include circadian changes in components of the immune system, e.g., lymphocytes, and circadian variation in primary and secondary immune responsiveness. The observation that many of these rhythms are inversely correlated to the glucocorticoid rhythm has led to the suggestion that fluctuations in the immune system may be a result of the glucocorticoid circadian rhythm. This study was designed to see if thymosin-alpha 1 (Tsn-alpha 1), a 28-amino acid polypeptide isolated from bovine thymus that has been reported to influence thymocyte differentiation, might follow a circadian rhythm, and thus play a role in the periodicity of the immune system. In these experiments, groups of 10 C57BL/6 or Swiss Webster mice were sacrificed at 4- or 6-hr intervals over a 24-hr period. Serum Tsn-alpha 1 and corticosterone levels were determined by radioimmunoassay. Results from the first experiment showed that Tsn-alpha 1 undergoes a circadian rhythm (p less than 0.001) with an acrophase (time of peak levels) 1.5 hr after the onset of light, and an amplitude (amount of maximum variation from the 24-hr mean) of 0.493 ng/ml Tsn-alpha 1-like immunoreactivity. These results were confirmed in an experiment in which the animals were placed on a reversed light cycle. In a separate experiment, the Tsn-alpha 1 circadian rhythm persisted in mice thymectomized 6 mo. earlier. In this latter experiment, a significant increase in the amplitude of the corticosterone rhythm in the thymectomized relative to sham-operated controls was also observed. Although these experiments do not imply casuality, it is interesting that the time of peak Tsn-alpha 1 levels can be correlated with the time of optimal immune function.     

Effects of constant darkness and constant light on circadian organization and reproductive responses in the ram

The relationship between circadian rhythms in the blood plasma concentrations of melatonin and rhythms in locomotor activity was studied in adult male sheep (Soay rams) exposed to 16-week periods of short days (8 hr of light and 16 hr of darkness; LD 8:16) or long days (LD 16:8) followed by 16-week periods of constant darkness (dim red light; DD) or constant light (LL). Under both LD 8:16 and LD 16:8, there was a clearly defined 24-hr rhythm in plasma concentrations of melatonin, with high levels throughout the dark phase. Periodogram analysis revealed a 24-hr rhythm in locomotor activity under LD 8:16 and LD 16:8. The main bouts of activity occurred during the light phase. A change from LD 8:16 to LD 16:8 resulted in a decrease in the duration of elevated melatonin secretion (melatonin peak) and an increase in the duration of activity corresponding to the changes in the ratio of light to darkness. In all rams, a significant circadian rhythm of activity persisted over the first 2 weeks following transfer from an entraining photoperiod to DD, with a mean period of 23.77 hr. However, the activity rhythms subsequently became disorganized, as did the 24-hr melatonin rhythms. The introduction of a 1-hr light pulse every 24 hr (LD 1:23) for 2 weeks after 8 weeks under DD reinduced a rhythm in both melatonin secretion and activity: the end of the 1-hr light period acted as the dusk signal, producing a normal temporal association of the two rhythms. Under LL, the 24-hr melatonin rhythms were disrupted, though several rams still showed periods of elevated melatonin secretion. Significant activity rhythms were either absent or a weak component occurred with a period of 24 hr. The introduction of a 1-hr dark period every 24 hr for 2 weeks after 8 weeks under LL (LD 23:1) failed to induce or entrain rhythms in either of the parameters. The occurrence of 24-hr activity rhythm in some rams under LL may indicate nonphotoperiodic entrainment signals in our experimental facility. Reproductive responses to the changes in photoperiod were also monitored. After pretreatment with LD 8:16, the rams were sexually active; exposure to LD 16:8, DD, or LL resulted in a decline in all measures of reproductive function. The decline was slower under DD than LD 16:8 or LL.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of zinc-aspartate and zinc-glycinate in healthy rats and on reserpine-induced gastric lesions

Experimental studies performed on 227 rats showed that Zn-aspartate and Zn-glycinate administered ip lowered the incidence, number, and severity of the reserpine-induced gastric lesions ensuring significant protection indices. Histochemical methods revealed increased amount of mucosal glycoproteins. The activity of dehydrogenases involved in energy metabolism that modulates acid secretion in the parietal cells was depressed. RNA content in the chief cells as premises of pepsinogen synthesis, was decreased. ATPase reaction in the periglandular capillaries was uniform and stronger, showing an improvement of gastric mucosal microcirculation. Since these histochemical changes were also noted in healthy rats receiving Zn salts, it might be suggested that they are not the mere expression of an anti-ulcer protective effect of zinc, but rather reflect its mechanism of action, relating to the complex metabolic events induced by the trace element. Our results are in agreement with those previously reported concerning the noxious influence of Zn depletion, the accelerated healing of peptic ulcer patients after Zn treatment, and the protective effect of Zn against ulcerogenesis in several experimental models involving different pathomechanisms.     

Effect of Helicobacter pylori eradication on peptic ulcer disease complicated with outlet obstruction

Background. At present, the prevalence of Helicobacter pylori ( H. pylori ) in complicated peptic ulcer and the effect of H. pylori eradication on complicated peptic ulcer have not been fully established. In this study, we report the prevalence of H. pylori in peptic ulcer patients complicated with gastric outlet obstruction, effectiveness of oral eradication therapy on these patients, and their long-term follow up.
Patients and Methods. Ten consecutive patients presenting with clinically and endoscopically significant obstructed peptic ulcers were included in this study. During each endoscopy, seven gastric biopsy specimens were obtained and analyzed for H. pylori colonization.
Results. The antral mucosal biopsy specimens were positive for H. pylori in nine patients. H. pylori infection was eradicated and complete ulcer healing was observed in all patients. The mean follow-up period was 14 (7–24) months. One patient had duodenal perforation and underwent surgical intervention following medical treatment, despite the eradication of H. pylori. Ulcer recurrence was noted in two (22.2%) of nine patients, and in one of them the recurrent ulcer was complicated with obstruction (11.1%). The mean time to ulcer recurrence was 17 months (range, 10–24 months). The biopsies and CLOtests were H. pylori negative at the time of ulcer or erosion recurrence in two patients.
Conclusion. We suggest that H. pylori eradication may improve the resolution in obstructive ulcer cases with colonization.     

The distribution of 4-hydroxynonenal-modified proteins in gastric mucosa of duodenal peptic ulcer patients

This study used monoclonal antibody specific for 4-hydroxynonenal (HNE)-histidine to evaluate immunohistochemical distribution of HNE-protein adducts in gastric mucosa biopsies of 52 peptic ulcer patients (all positive for H. pylori) and of 20 healthy volunteers (eight positive and 12 negative for H. pylori). HNE-modified proteins were present in glandular epithelium in all subjects, both patients with duodenal peptic ulcer and healthy subjects. Hence, the presence of HNE did not appear to be related to the presence of H. pylori. However, in patients with duodenal peptic ulcer accumulation of HNE-protein adducts was frequently observed also in nuclei, while in the control group such subcellular distribution of HNE was not observed at all. This study shows physiological presence of HNE in human gastric mucosa, but also suggests its role in pathology of gastric dysfunction in duodenal peptic ulcer patients manifested by accumulation of HNE-protein adducts in particular in nuclei of gastric glandular epithelium.     

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

Field survey of circadian rhythm in PEF of electronics workers suffering from colophony-induced asthma

Twenty-two British electronics workers suffering from occupationally-induced asthma due to their exposure to colophony fumes self-recorded their peak expiratory flow (PEF) every 1-2 hr throughout the waking span for at least two weeks, both during work and vacation periods. Data were analyzed by a two-step procedure using the statistical techniques of Single and Population Mean Cosinor analyses. The objective endpoints of mesor (24-hr mean), amplitude (measure of 24-hr rhythmic variation) and acrophase (peak time along the scale of 24 hr) for the time-spans of the work-week (Monday-Friday), weekend after work (Saturday-Sunday) and vacation weekdays and vacation weekends were compared. The PEF data of four workers who participated in the study for nearly one year also were evaluated for seasonal variation. A statistically significant difference (P less than 0.04) was detected in the PEF amplitude between work and vacation weeks; the difference in the PEF mesor and acrophase between work-weekdays and work-weekends achieved near or statistical significance (P = 0.07 and 0.05, respectively). The at-work amplitude was higher and the acrophase earlier timed. There was no statistically significant difference between work-week and weekend-after-work PEF mesors. Winter PEF mesors were significantly lower than summer ones in the four subjects self-measuring their bronchial patency over the year. Overall, the findings indicate that data obtained through employee surveys, using lightweight portable and inexpensive PEF Wright meters and analyzed by statistical analyses used in the field of biological rhythm research, yield objective evidence of occupationally associated decrements in pulmonary function resulting from colophony fume exposure.     

Mutants of the Biological Clock in CHLAMYDOMONAS REINHARDI

A genetic analysis of the biological clock in Chlamydomonas reinhardi has been initiated. Of six wild-type strains tested (3 mt(+) and 3 mt(-)), five had periods close to 24 hr whereas one had a 21-hr period. Mutants with altered clock period have been isolated. The periods of 3 of these variant strains are temperature compensated. Genetic crosses involving a long-period mutant suggest that a single gene confers the long-period character, and in general clock-period length seems to be a useful phenotypic measure of alterations in the clock due to genetic differences. One phase mutant was found but its behavior was variable and the phase of the rhythm, relative to a light-dark transition which initiates the rhythm, does not seem to be reliable as a parameter of clock differences. No markers have yet been mapped.     

Circadian rhythm of serotonin binding in rat brain--II. Influence of sleep deprivation and imipramine

Sleep deprivation (SD) modified the circadian rhythm of specific high affinity serotonin (5-HT) binding to rat brain membranes. In control rats a 24-hr rhythm was evident with a trough at 1000-1200 and a nadir at 0000. During the last 26 hr of a 49 hr SD period, trough and peak values were delayed by 4-6 hr. The 24-hr mean binding was significantly (P less than 0.001) different from that of controls. If sleep deprivation was followed by recovery sleep (RS), the normal rhythm of 5-HT binding was obtained already within 1 hr after SD. The effects of SD and RS were ascertained by plasma ACTH and corticosterone assay. No significant change in the hormone rhythms were observed through the mean plasma level of ACTH and corticosterone were enhanced to about 180 and 150%, respectively. Chronic treatment with the antidepressant imipramine resulted in a decrease of the 24-hr mean 5-HT binding by about 50% and a 2-hr delay of peak and trough values. Imipramine treatment decreased the peak value of 5-HT concentration at 1000 to about 65% and appears to abolish the rhythm of 5-HT concentration.     

Glutathione system of erythrocyte and plasma in peptic ulcer

A complex study of the blood glutathione system has been carried out for the first time in patients with peptic (gastric and duodenal) ulcer. In erythrocytes and blood plasma of patients with the complicated peptic ulcer and postgastroresection syndromes there was the increase of conjugated dienes (and in the second group the increase in antioxidant activity). Under these conditions the main change was the sharp and identical decrease in glutathione peroxidase activity. In patients with uncomplicated peptic ulcer there was sharp increase in erythrocite and plasma glutathione reductase activity and plasma GSH. In operated but basically healthy patients plasma glutathione peroxidase remained decreased but plasma GSH sharply increased. Evidently complicated peptic ulcer is characterized by decreased functioning of the glutathione system. Activation of this system and the decrease or disappearance of manifestations of oxidative stress are associated with a favorable course of this disease, especially at uncomplicated peptic ulcer. The revealed changes significantly differ from those observed in patients with viral hepatitis, blle excretory diseases and strokes.     

The distribution of 4-hydroxynonenal-modified proteins in gastric mucosa of duodenal peptic ulcer patients

This study used monoclonal antibody specific for 4-hydroxynonenal (HNE)-histidine to evaluate immunohistochemical distribution of HNE–protein adducts in gastric mucosa biopsies of 52 peptic ulcer patients (all positive for H. pylori) and of 20 healthy volunteers (eight positive and 12 negative for H. pylori). HNE-modified proteins were present in glandular epithelium in all subjects, both patients with duodenal peptic ulcer and healthy subjects. Hence, the presence of HNE did not appear to be related to the presence of H. pylori. However, in patients with duodenal peptic ulcer accumulation of HNE-protein adducts was frequently observed also in nuclei, while in the control group such subcellular distribution of HNE was not observed at all. This study shows physiological presence of HNE in human gastric mucosa, but also suggests its role in pathology of gastric dysfunction in duodenal peptic ulcer patients manifested by accumulation of HNE-protein adducts in particular in nuclei of gastric glandular epithelium.     

Circannual variation of intestinal cell proliferation in BDF1 male mice on three lighting regimens

BDF, male mice were studied over a 24-hr span in winter, spring, summer and fall. For three weeks prior to study, one-third of the animals were kept under a lighting regimen of 8 hr light alternating with 16 hr of darkness (LD 8:16), one-third on a lighting regimen of LD 12:12 and a remainder on a lighting regimen of LD 16:8. During each study, subgroups of animals on all three lighting regimens were killed at 4-hr intervals over a 24-hr span. Twenty minutes prior to being killed, the animals received 5yCi of [³Hthymidine/0.2 ml/20 gm of body weight intraperitoneally. The thymidine uptake in the DNA of the colon and of the small intestine were studied as an index of cell proliferation. A circadian rhythm in [³H]-thymiduie uptake in the colon was found and validated by cosinor analysis. This rhythm was similar in acrophase and amplitude in the animals kept on LD 8:16 and LD 12:12. Also in the mice on LD 16:8, there was a statistically significant circadian rhythm of ('HJ-thymidtne uptake in the DNA of the colon during all four seasons. The acrophases of this rhythm, however, varied widely suggesting free running. A circadian rhythm of pHJ-thymidine uptake in small intestine was less consistent. In animals on all three lighting regimens, however, a circannual variation of f'HJ-thymidine uptake in DNA in colon and small intestine was found with the highest uptake during summer. This study indicates that a lighting regimen of LD 16:8 does not reliably synchronize the circadian rhythm of [³H]-thymidine uptake in the colon. It further shows a circannual rhythm of this function in the colon and in the small intestine which persists under three lighting regimens (LD 8:16, 12:12 and 16:8) maintained for three to four weeks prior to being killed.