Terms Of Necrosis Research Articles

Effectiveness of Hypericum perforatum Extract in the Treatment of Corrosive Esophageal Burns

Purpose The purpose of our study is to determine the effectiveness of “Hypericum perforatum” extract in corrosive esophageal burns and to shed light on the search for new treatments. Materials and methods A total of 32 Sprague Dawley rats were separated into 4 groups. A standard esophageal burn model was created. Group 1 was identified as the sham group. Group 2 was burned and no treatment was performed afterward. Group 3 was burned and then 2 cc/day H. perforatum extract was given for 21 days. Group 4 was not applied any process and 2 cc/day H. perforatum extract was given for 21 days. The rats were sacrificed and biopsy specimens were taken for histopathological examination for the presence of inflammation, fibrosis, and necrosis. Results There was a significant difference between groups in terms of inflammation, fibrosis, and necrosis. Furthermore, in the bilateral comparisons between the groups, there was a meaningful difference in terms of inflammation and fibrosis between Group 2 and Group 3. However, there was no meaningful difference between the same groups in terms of necrosis. Conclusion H. perforatum extract may be effective on inflammation, fibrosis, and necrosis in corrosive esophageal burns.

Evaluation of Necrotic, Edematous and Inflammatory Changes in Bone Marrow and Soft Tissue After Irrigation with Different Concentrations of NaOCl Solution: An Experimental Study in Rat Tibia.

We aimed to investigate effects of different concentrations (0.5-5%) of Sodium Hypochlorite (NaOCl) solution on healthy tissues, and determine the optimal concentration that does not harm to tissue. 30 tibias of 15 male Wistar albino rats were used. The tibias were randomly divided into 5 groups (Salin, 0.5%, 1%, 2.5%, and 5% NaOCl). Tibias were reamed intramedullary, and irrigated with 20 ml of saline or increasing concentrations of (0.5-5%) NaOCl. The tibias were embedded in paraffin and the sections were stained with hematoxylin-eosin. All sections were assessed for edema, acute inflammation, or necrosis according to their density, in bone marrow and soft tissues. Pairwise comparisons revealed that irrigation of tibia with saline or 0.5% NaOCl solutions was not statistically significant in terms of necrosis in the bone marrows (p=0.320). However, irrigation of rat tibia with saline caused less necrosis in the bone marrows compared to high concentrations (1%, 2.5%, and 5%) of NaOCl (saline and 1% NaOCl, p=0.017; saline and 2.5% NaOCl, p=0.0007; saline and 5% NaOCl, p=0.001). As an irrigation solution, the effects of 0.5% NaOCl are similar to those of saline in terms of edema, inflammation, and necrosis. There is a need for evaluation of necrosis for extended periods such as one week or one month by immunohistochemical methods and flow cytometry.

Naturally Produced Lovastatin Modifies the Histology and Proteome Profile of Goat Skeletal Muscle

Simple SummaryEnteric methane formation in ruminants is one of the major contributors to climate change. Among the potential strategies, the supplementation of naturally produced lovastatin has been reported as one of the promising approaches for the mitigation of methane emissions. Nevertheless, statins have been associated with the development of muscle-related adverse effects which could affect the health and wellbeing of the animals. We have reported previously that supplementation of naturally produced lovastatin at 2 and 4 mg/kg body weight (BW), reduced methane emissions in goats without adversely affecting rumen fermentation and animal performance, except at higher level of lovastatin (6 mg/kg BW). However, the effects of lovastatin on the skeletal muscle in goats and the associated mechanisms have not been studied. Hence, the present study aimed to examine the effects of lovastatin on the histology of the goat skeletal muscle from the above study and to further elucidate the related underlying biochemistry processes. Histology analysis observed marked degeneration in the longissimus thoracis et lumborum muscle of goats supplemented with 6 mg lovastatin/kg BW. Our preliminary label-free proteomics analysis identified approximately 400 proteins in total, a number of which were differentially expressed, which are involved in energy metabolism and may have contributed to the observed skeletal muscle damage above 4 mg/kg BW.This study was conducted to examine the effects of different levels of lovastatin on the histological and sarcoplasmic proteome profile of goat skeletal muscle. A total of 20 intact male Saanen goats were randomly assigned in equal numbers to four groups and fed a total mixed ration containing 50% rice straw, 22.8% concentrates and 27.2% of various proportions of untreated or treated palm kernel cake (PKC) to achieve the target daily intake levels of 0 (Control), 2 (Low), 4 (Medium) or 6 (High) mg lovastatin/kg BW. A histological examination discovered that the longissimus thoracis et lumborum muscle of animals from the Medium and High treatment groups showed abnormalities in terms of necrosis, degeneration, interstitial space and vacuolization. Our preliminary label-free proteomics analysis demonstrates that lovastatin supplementation induced complex modifications to the protein expression patterns of the skeletal muscle of the goat which were associated with the metabolism of carbohydrate and creatine, cell growth and development processes and other metabolic processes. The changes in these biochemical processes indicate perturbations in energy metabolism, which could play a major role in the development of myopathy. In conclusion, the present study suggests that supplementation of naturally produced lovastatin above 4 mg/kg BW could adversely affecting the health and wellbeing of treated animals.

Short-term histopathological effects of dienogest therapy on ovarian endometriomas: in vivo, nonrandomized, controlled trial

Ovarian endometriosis is a common gynecological disorder. To date, progestins are recommended as the first-line medical treatment for symptomatic ovarian endometriosis. The aim of this study was to evaluate the main histopathological effects of short-term dienogest therapy in patients with ovarian endometriomas scheduled for surgery. A prospective, nonrandomized controlled trial, including 70 symptomatic women with single ovarian endometriotic cyst (diameter between 30–50 mm) was conducted. Women scheduled for surgery were divided into two groups, depending on the treatment established at enrollment: 36 women received progestin therapy with dienogest (P group) and 34 women received no therapy (C group). At histopathological examination necrosis, inflammation, decidualization, glandular atrophy and angiogenesis were blindly evaluated. At tissue level, decidualization was significantly more frequent in P group compared to C group (p = .001). A nonsignificant tendency (p = .29) towards a slight decreased inflammation in P group was found. No significant differences were observed between the two groups in terms of necrosis, glandular atrophy and angiogenesis. The study suggests that high decidualization rate and the tendency to reduced inflammatory reaction in the short-term administration of dienogest might contribute to its therapeutic efficacy.

Surgical Complications in 1408 Primary Cleft Palate Repairs Operated at a Single Center in Guwahati, Assam, India.

To analyze surgical complications after primary cleft palate repair in a setting with limited resources. A total of 1608 consecutive cleft palate repairs with 1408 follow-ups, operated upon between 2011 and 2013, were reviewed retrospectively through medical records. Patients were 10 months to 50 years old at the time of surgery, with a median age of 9 years. Guwahati Comprehensive Cleft Care Center, Guwahati, India. Primary cleft palate repair. Postoperative complications in terms of necrosis, dehiscence, fistula, infection, and "hanging palate" were assessed, as was perioperative bleeding. Logistic regression was used with complication (yes/no) as the binary dependent variable and with age, cleft type, and surgeon (visiting/long-term) as covariates. The overall incidence of postoperative complications was 16.9% with a fistula rate of 13.6%. The incidence of perioperative bleeding was 1.8%. Logistic regression analysis identified cleft severity (P ≤ .001) and visiting surgeon (P ≤ .01) as factors related to the incidence of postoperative complications. Age at surgery was related to both the incidence of postoperative complications (P ≤ .001) and perioperative bleeding (P < .05). Due to increased risks of surgical complications, older patients with complete clefts should only be operated upon after careful consideration. In addition, these patients should be assigned to surgeons experienced with this cleft type.

Duration of injury correlates with necrosis in caerulein-induced experimental acute pancreatitis: implications for pathophysiology.

Pancreatic acinar cell necrosis is indicative of severe pancreatitis and the degree of necrosis is an index of its outcome. We studied whether the dose and duration of injury correlates with severity, particularly in terms of necrosis, in caerulein-induced acute pancreatitis (AP) in Swiss albino mice. In addition to control group 1 (G1), groups 2 and 3 received four injections of caerulein every hour but were sacrificed at five hours (G2) and nine hours (G3) respectively, and group 4 received eight injections and was sacrificed at nine hours (G4). The severity of pancreatitis was assessed histopathologically and biochemically. The histopathological scores of pancreatitis in groups 3 and 4 were significantly higher than in groups 1 and 2 (4 vs. 1, 4 vs. 2, 3 vs. 1, 3 vs. 2; P<0.05). TUNEL-positive apoptotic cells were significantly higher in groups 2 and 3 compared with groups 1 and 4 (P<0.05). Necrosis was significantly more in group 4 than other groups (37.49% (4.68) vs. 19.97% (1.60) in G2; 20.36% (1.56) in G3; P=0.006 for G 2 vs. 4 and P=0.019 for G 3 vs. 4). Electron microscopy revealed numerous autophagosomes in groups 2 and 3 and mitochondrial damage and necrosis in group 4. The pancreatic and pulmonary myeloperoxidase activity in group 4 was significantly higher than that in the other groups (P<0.01). Hence, severity of pancreatitis is a function of the dose of injurious agent, while inflammation is both dose and duration dependent, which may also explain the wide spectrum of severity of AP seen in clinical practice.

Effects of local phenytoin on seroma formation after mastectomy and Axillary lymph node dissection: an experimental study on mice

BackgroundSeroma formation is the most common complication after breast cancer surgery. It is an important complication since it prolongs therapy duration, increases cost, and negatively affects patient psychology. Currently, there is no widely accepted method that prevents seroma formation. We tried to investigate impact of local phenytoin application on seroma formation following an experimental mastectomy model created in rats.MethodsTwo groups including eight rats in each were randomized. Saline injection was applied in the first group, whereas 1% phenytoin was locally used in the second group. Ten days after the surgery, seroma formation and wound-healing processes were evaluated using histopathological and biochemical examinations.ResultsPhenytoin significantly decreased seroma formation. Fibrosis was significantly increased and angiogenesis was significantly reduced in the phenytoin group (P < 0.05). Increased levels of macrophage and lymphocyte infiltration was detected in the control group (P < 0.05). No difference was detected between the groups in terms of necrosis, edema, congestion, and PNL (Polymorphonuclear leucocyte) and fibroblast infiltration.ConclusionsSeroma formation-reducing effect of phenytoin might have occurred over its anti-inflammatory, anti-angiogenetic, and fibrosis augmenting effects.

Potentiation of amyloid-β peptide neurotoxicity in human dental-pulp neuron-like cells by the membrane lipid peroxidation product 4-hydroxynonenal

Lipid peroxidation is generally considered as primarily implicated in the pathogenesis of Alzheimer's disease (AD); one of its more reactive end products, 4-hydroxynonenal (HNE), has been shown to cause neuron dysfunction and degeneration. HNE production in the brain is stimulated by the amyloid-β peptide (Aβ), whose excessive accumulation in specific brain areas is a hallmark of AD. Conversely, Aβ production is up-regulated by this multifunctional aldehyde. Findings reported here point to the ability of HNE and Aβ to interact, with consequent potentiation of Aβ’s cytotoxicity as determined in vitro using neuron-like cells derived from human dental-pulp progenitor cells. Preincubation of cells with the aldehyde markedly up-regulated Aβ uptake and intracellular accumulation, by overexpressing two of the three components of the plasma membrane multireceptor complex CD36/CD47/β1-integrin: experimental and clinical data indicate that intraneuronal accumulation of Aβ is an early event possibly playing a primary role in AD pathogenesis. That HNE-mediated overexpression of CD36 and β1-integrin, which plays a key role in HNE's potentiating Aβ neurotoxicity, in terms of necrosis, was confirmed when this effect was prevented by specific antibodies against the two receptors.

Correlation of MTDH/AEG-1 and HOTAIR Expression with Metastasis and Response to Treatment in Sarcoma Patients

Chemoresistance and metastasis are the main reasons for the failure of current treatments with sarcoma patients. Novel biomarkers are required to predict metastasis and response to treatment. The oncogene MTDH/AEG1 and the long noncoding RNA (lincRNA) HOTAIR are two novel factors involved in drug resistance and metastasis in various types of solid tumors. However, the correlation between MTDH/AEG-1 and HOTAIR expression with metastasis and drug resistance in sarcoma is unknown. Expression of MTDH protein or HOTAIR was detected by Western blotting or qRT-PCR, respectively, in primary and metastatic sarcoma patient tissue samples. High individual or co-expression of MTDH/AEG1 and HOTAIR was observed in three of four primary and six of eight metastatic sarcoma patient tumor samples. High level expression of both of MTDH/AEG1 and HOTAIR in the primary tumor correlated with a likelihood to metastasize. MTDH expression was lower in samples pre-treated with irradiation and/or chemotherapy as compared to those that had not been treated. HOTAIR expression seemed to correlate with the percent necrosis seen in different sarcoma samples. High levels of both MTDH/AEG-1 and HOTAIR in primary sarcoma are correlated with a high probability of metastasis. By contrast, reduced expression of both MTDH/AEG-1 and HOTAIR is correlated with a good response to treatment in terms of necrosis, suggesting that levels of MTDH and HOTAIR are potential biomarkers for treatment efficacy. Whether we can predict disease progression in sarcoma remains to be seen. Additional study is needed to better define the best clinical application of MTDH/AEG-1 and HOTAIR expression with metastasis and outcome.

Potential Role of FDG PET Imaging in Predicting Metastatic Potential and Assessment of Therapeutic Response to Neoadjuvant Chemotherapy in Ewing Sarcoma Family of Tumors

The aim of this study was to retrospectively correlate FDG uptake in primary Ewing sarcoma family of tumors (ESFT) with tumor behavior, and to evaluate whether FDG PET can be used to predict response to neoadjuvant chemotherapy (NACT) in this patient group. Out of the total 54 patients of recently diagnosed ESFT who underwent pretreatment FDG PET imaging, group I included patients without metastasis at presentation (n = 34) and group II included those with metastasis at presentation (n = 20). Fourteen of these patients had undergone FDG PET after 4 cycles of induction chemotherapy and surgical resection of primary tumor. In this subgroup of 14 patients, maximum standardized uptake value (SUVmax) of primary tumor was estimated before and after 4 cycles of induction chemotherapy and was correlated with the histopathological response in terms of necrosis in the tumor specimen. Mean SUVmax in the primary tumor in group I patients was 6.84 and in group II patients, it was 11.31. The difference between mean SUVmax of these 2 groups was significant by Wilcoxon test analysis, with P < 0.01. In group II patients, SUVmax in metastasis with maximum FDG uptake was consistently lower as compared with that of primary tumor. In subgroup of 14 patients, Pearson correlation analysis showed that percentage change in SUVmax of primary tumor correlated well with percentage necrosis on histopathological examination (P < 0.01). FDG uptake in primary ESFT reflected its metastatic potential and hence the aggressive behavior. The significant correlation between change in metabolic activity of the primary tumor and histopathological response after neoadjuvant chemotherapy suggests that FDG PET may be an ideal noninvasive method to assess tumor behavior and response to therapy in ESFT.

A Comparative Study of Using a Combination of Calcium Chloride and Mineral Trioxide Aggregate as the Pulp-capping Agent on Dogs’ Teeth

Introduction The addition of some chemicals to mineral trioxide aggregate (MTA) may improve the physical properties of the biomaterial. The aim of this study was to compare a combination of MTA with/without CaCl 2 as pulp-capping agents in dogs’ teeth. Methods The dental pulp of 32 teeth in four dogs were exposed and capped with either MTA or MTA/CaCl 2. After 2 months, the animals were sacrificed, and the teeth were prepared for histological evaluation. Pulpal response to the two capping materials was evaluated in terms of necrosis, inflammation, and formation of a calcified bridge. The chi-square test was used for data analysis. Results Histological results showed a higher percentage of inflammation and necrosis and a lower percentage of calcified bridge formation in MTA/CaCl 2 samples compared with MTA; however, the differences were not statistically significant ( P > .05). Conclusions The addition of CaCl 2 to MTA pulp-capping agent did not improve the properties of this biomaterial.

3-D Visualization of Acute RF Ablation Lesions Using MRI for the Simultaneous Determination of the Patterns of Necrosis and Edema

Catheter ablation using RF energy is a common treatment for atrial arrhythmias. Although this treatment provides a potential cure, currently, there remains a high proportion of patients returning for repeat ablations. Electrophysiologists have little information to verify that a lesion has been created in the myocardium. Temporary electrical block can be created from edema, which will subside. MRI can visualize acute and chronic ablation lesions using delayed-enhancement techniques. However, the ablation patterns cannot be determined from 2-D images alone. Using the combination of T(2)-weighted and delayed-enhancement MRI, ablation lesions can be characterized in terms of necrosis and edema. A novel 3-D visualization technique is presented that projects the image intensity due the lesions onto a 3-D cardiac surface, allowing the complete, simultaneous visualization of the delayed-enhancement and T(2)-weighted ablation patterns. Results show successful visualization of ablation patterns in 18 patients, and an application of this technique is presented in which electroanatomical mapping systems can be validated by overlaying the acquired ablation points onto the cardiac surfaces and assessing the correlation with the lesion maps.

The protective effect of erythropoietin infusion on testicular torsion/detorsion: an experimental study

The aim of the present study was to evaluate the effects of erythropoietin (EPO) on the histopathology of testes after unilateral testicular torsion and detorsion. Twenty-five male Sprague-Dawley rats weighing 120 g were used in this study. The rats were randomly divided into three groups, a sham group consisting of five rats and the other two groups consisting of ten rats. In group 1 (sham group), right orchiectomy with no additional intervention was performed. In group 2 (T/D group), torsion was created by rotating the testis 720 degrees in a clockwise direction for 4 h. After a 4-h torsion period, the right testis was detorted and replaced into the scrotum for 4 h. After the torsion, 0.5 cc 0.9% NaCl solution was injected once and three times in a week (total 12 doses). In group 3 (T/D + erythropoietin; EPO group), the same surgical procedure was done as in group 1, but EPO 1,000 IU/kg was injected just before the detorsion and three times in a week. At the end of each procedure, bilateral orchiectomies were performed for the histopathological examinations in all groups. We examined the testes weight, vascularization of the region between the seminiferous tubules, percentage of necrotic seminipherous tubules, and maturation of spermatogenesis in terms of necrosis, sertoli cells, maturation arrest of spermatogenesis, hypospermatogenesis, and normal spermatogenesis of torsioned testis tissues with and without EPO treatment. Extremely significant differences in testicular weight were observed in group 1 compared to groups 2 and 3 (P < 0.001). Administration of EPO significantly influenced the rescue of testicular function by preserving the intact seminiferous tubular morphology, lowering the percentage of necrotic seminipherous tubules, and significantly reducing histological damage (P < 0.05).

Opposed bilateral transposition flap: a simple and effective way to close large defects, especially of the limbs

Excision of large tumours, particularly of the limbs, can be challenging because of problems related to wound repair. This is especially true of the lower legs, where skin is often tight and difficult to mobilize. Closure by flap, which would represent the first choice for defects usually between 12-15 mm to 38-40 mm diameter, is at risk of developing complications, such as end-flap necrosis or dehiscence due to skin tension. For larger defects, usually more than 40 to 45 mm diameter, grafting still remains the only realistic option in the majority of cases, with all the various problems associated with this procedure, such as lengthy healing times and the risk of developing leg ulcers, above all in elderly patients with impaired blood circulation. Second intention healing implies extraordinarily long healing times with often unacceptable delays in normal ambulation and activity. To find an alternative to the usual repair techniques and to try to reduce the risk of complications. We developed a relatively simple but effective technique for the closure of large wounds resulting from the excision of tumours. Our technique consists of two longitudinal, parallel, transposition flaps obtained from two opposite sides of the wound, with major axes orientated in the cephalic-caudal direction. The two flaps are then rotated around two fulcra placed at two extremes of the wound by approximately 90 degrees . This relatively simple technique has never caused any of the ordinarily associated problems in terms of necrosis or ulcer development. In addition, dehiscence of sutures never occurred, given the fact that suture tension is minimal. Quick healing has resulted in the majority of cases, avoiding all the problems associated with grafting or other traditional flap techniques.

CC-chemokine activation in acute pancreatitis: enhanced release of monocyte chemoattractant protein-1 in patients with local and systemic complications.

Systemic leukocyte activation is claimed to trigger inflammatory response and remote organ dysfunction in acute pancreatitis. Chemokines are inflammatory mediators with potent leukocyte-activating properties and have been shown to be involved in the pathophysiological process of experimental acute pancreatitis. However, as little is known about their role in human disease we investigated local and systemic concentrations of different CC-chemokine members in patients with acute pancreatitis. We included 68 patients with acute pancreatitis in the present study. Local complications in terms of necrosis were present in 37 (54%) patients of whom 21 (57%) developed pancreatic infections. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta) concentrations were measured daily over 2 weeks after study inclusion by ELISA in sera and lesser sac aspirates. MCP-1 serum concentrations showed a dramatic increase in patients who developed local complications and/or remote organ failure. Herein, a close correlation was found between the severity of remote organ failure and the degree of MCP-1 elevation. Multiple regression analysis identified pancreatic infections as well as renal and cardiocirculatory failure as independent variables associated with enhanced systemic MCP-1 release. MIP-1alpha levels remained unaffected by local complications and showed a significant increase only; if multiple organ dysfunction syndrome (MODS) developed or patients subsequently died. In contrast, MIP-1beta concentrations correlated with neither the presence nor the severity of any complication. Compared with systemic concentrations, local lesser sac aspirates revealed significantly higher levels of MCP-1, whereas MIP-1alpha and MIP-1beta were not different. Complicated acute pancreatitis is associated with significantly elevated local and systemic concentrations of the CC-chemokine MCP-1. Our results suggest that, among the CC-chemokine members investigated, MCP-1 might play a pivotal role in the pathological mechanism of complicated acute pancreatitis.

Effect of cumulative courses of intraarterial cis-diamminedichloroplatin-II on the primary tumor in osteosarcoma.

Preoperative chemotherapy with intraarterial cis-diamminedichloroplatin-II (CDP) and mannitol diuresis was administered to the primary tumor in 42 patients with osteosarcoma. The dose was 150 mg/m2 and more than 90% of the infusions were administered during a 2-week period. On occasion this period was extended to 3 weeks because of temporary renal insufficiency or logistical circumstances. Definitive surgical specimens were prepared by means of an arteriogram-directed plane of dissection with mapping and random sections. Histologically, tumor destruction was evaluated in terms of necrosis, inflammatory response, and fibrovascular regeneration. Quantification of the percent of tumor necrosis was as follows: less than 40% (consistent with spontaneous necrosis and/or no chemotherapy effect); 40% to 60% (possible chemotherapy effect); 60% to 90% (chemotherapy effect--partial response); and 90% to 100% (complete response). Therapeutic efficacy also was correlated with the number of CDP courses (one to three, four to five, and six to seven) and tumor subtype. Significant therapeutic effect (greater than 60% destruction) was observed with four or more CDP courses (one of nine tumors [one to three courses] versus 26 of 33 tumors [four to seven courses] [P = 0.01]). More than 60% of the tumor destruction was observed in the following subtypes: osteoblastic (22 of 28), fibroblastic (three of six), and telangiectatic (two of five). These data demonstrate that four or more courses of intraarterial CDP are required to achieve optimum effects and that osteoblastic osteosarcoma is highly responsive.

Limb Salvage in Osteogenic Sarcoma of Extremities: A New Therapeutic Approach Associating Infusion and Hyperthermic Antiblastic Perfusion

(J. Extra-Corpor. Technol. 19[3] p. 338-347 Fall 1987, 49 ref.) From August 1983 to September 1986, 17 patients affected by osteogenic sarcoma of extremities were admitted to our Division with only surgical alternatives of amputation or disarticulation due to the impressive local extension of disease. Trying to avoid this procedure we started a program of limb salvage as follows: two cycles of intraarterial cis-platinum (CCDP) plus systemic high dose of methotrexate (HDMTX) followed by hyperthermic antiblastic perfusion (HAP) with high dose COOP and for the majority of patients 2 more cycles of systemic HDMTX + COOP with or without radiotherapy on the primary. Immediate response, evaluated both in terms of necrosis and of clinical and radiologic reduction of the tumor mass, was so impressive that in 10 patients it was possible to perform a conservative surgery, en bloc resection of the primary tumor plus endoprosthesis, with a satisfactory functional and cosmetic result. None ofthe patients relapsed locally; 8 developed lung metastases that, whenever possible, were resected.

Effect of thioacetamide on the incorporation of [3H]-thymidine into DNA of 13 tissues and on the mitotic index of the corneal epithelium of BD2F1 in male mice while taking into consideration circadian variation.

An investigation was done to assess the effect of a single intraperitoneal (ip) injection of thioacetamide on the incorporation of [3H]TdR into DNA of 13 different tissues and on the mitotic index of the corneal epithelium of mice. Seven-week-old CD2F1 mice, who had been standardized to 12 hours (hr) of light alternating with 12 hr of darkness, and fed ad libitum were used. The experimental design took into consideration the circadian variation that characterizes cell proliferation in all of the tissues studied. This was done by killing subgroups of seven animals every 6 hr for 96 hr. Thirty minutes prior to killing all mice were injected ip with 25 mu Ci of [3H]-thymidine and its incorporation into DNA was determined. The tissues of all thioacetamide and saline treated mice showed marked circadian variation in DNA synthesis. Thioacetamide treatment brought about significant (P less than 0.05) stimulation of DNA synthesis in the liver and kidney thus confirming, but extending an earlier finding. Moreover, the data showed for the first time that DNA synthesis in the bone marrow and spleen and colon were markedly statistically significantly stimulated at specific times after treatment. Synthesis of DNA in the thymus, lung, testes, tongue, esophagus, duodenum, rectum and the mitotic index in the corneal epithelium were not statistically significantly altered by thioacetamide treatment. A preliminary study also was carried out to explore what effect multiple treatment with epidermal growth factor (EGF) had on DNA synthesis in thioacetamide treated mice. Mice were killed 36 hr after thioacetamide treatment, but were treated with EGF which began 15 hr after the thioacetamide was administered and this was repeated at 18, 21 and 24 hr (50 micrograms/mouse/treatment). Under the conditions of this study EGF significantly (P less than 0.05) depressed DNA synthesis 76% in the liver, 64% in the thymus, 22% in the spleen, 30% in the duodenum and 24% in the esophagus. A histological analysis of the livers of four EGF treated and four non-EGF treated mice was done, but no consistent differences in terms of necrosis, inflammation or regeneration were observed between the two groups.