Role of MLL3 in regulating cardiac stem cells following cardiac cachexia.

OBJECTIVE: Cardiac cachexia is a form of serious illness that results with terminal stage of heart failure. It is associated with unreasonable weight loss and muscle loss with poor prognosis. Cardiac stem cells play a major role in repairing, damaged cardiac tissue and they are regulated by different mechanisms. In the present study, we investigated the role of MLL3 in regulating cardiac stem cells following cardiac cachexia. MATERIALS AND METHODS: To effectively study the cardiac cachexia, we established a Dahl rat model that produces symptoms similar to cachexia. Using histology, we analyzed the acute and chronic stage of cardiac cachexia. Immunohistochemistry and Western blotting were used to analyze the expression of MLL3 and Oct-4. RESULTS: The rat develops an acute form of cachexia after 2 months of fed with high-salt (8% NaCl) diet, which is characterized by inflammation and tissue damage that are observed through the histological sectioning. The chronic cardiac cachexia developed after 5 months of high-salt diet and histologically it shows tissue loss. At the molecular level the stem cell marker, Oct-4, shows elevated expression at acute stage, but down regulated latter in the chronic stage of cardiac cachexia. Also, MLL3 shows a similar pattern of upregulated expression in acute stage of cachexia, but significantly down regulated in the chronic stage of cachexia that implies their role in regulating the cardiac stem cell and their proliferation. CONCLUSIONS: Our results show that the cardiac stem cells in association with MLL3 support in maintaining homeostatic after initial pathological stages of cachexia but not in the chronic stage of cachexia.

Epidemiologic survey on organophosphate-induced delayed polyneuropathy (OPIDP) among patients recovered from Methamidophos poisoning.

As Methamidophos (MAF) is currently responsible for half of the pesticide intoxications and fatality cases in China, the need to assess the frequency and the characteristics of the OPIDP among the victims who recovered from MAF poisoning is obvious. One-hundred and four subjects suffering from MAF intoxication were selected according to their medical records in the local rural hospitals in the Mu-du suburb of Su-Zhou, and the Shi-Qiu suburb of Nanjing. Face-to-face interviews were performed during home visits to all selected subjects, with the only exception of 4 patients. In those cases, information was provided by their kin relatives. Fourteen cases of delayed polyneuropathy (OPIDP) were identified: all patients who suffered from OP poisoning and had OPIDP showed a typical clinical course. The overall incidence of OPIDP was surprisingly high: 13.5%. The risk of OPIDP was associated with the severity of the intoxication. No association was found between OPIDP incidence and sex, age or treatment with dexametholone during the acute phase of the disease (RR = 0.98, p = 0.79). All 14 cases of OPIDP recovered in one and a half year without any permanent disability.

Antidotal effect of glucoside extracted from Astragalus membranaceus on dimethoate intoxication in guinea pigs.

Therapeutic effect of the glucoside extracted from the root of Astragalus Membranaceus (AM) was studied in guinea pigs intoxicated with 600 mg/kg doses of Dimethoate (D). Four groups of guinea pigs, each consisting of two males and two females, were treated with (a) D, (b) D + Atropine, and (c) D + AM, (d) D + Atropine + AM. The survival time of the animals increased from an average of 70 minutes without AM to an average of 235 minutes with AM. Severe changes in ECG were observed prior to respiratory distress in groups without AM, and Atropine did not modify such changes. Differently, severe ECG disorders appeared only after respiratory distress in groups treated with AM. Prolongation of the Q-T interval and changing of the T wave configuration were significantly mitigated in the AM treated animals, while, arrhythmias were minimized and postponed. Moreover, muscular fasciculation and fibrillation, seizures and secretion in the respiratory tract were also significantly reduced by AM treatment. Results have shown that AM could be a promising drug to be used after cholinergic crisis in the treatment of cardiac complications with severe organophosphate intoxication.

Health effects of pesticides: a review of epidemiologic research from the perspective of developing nations.

Acute poisoning among pesticide applicators is still a prominent health hazard in rural areas in developing countries, but published reports are very rare. Registration analysis and descriptive study are helpful in giving guidance for orientation and evaluation of preventive strategies and measures. Data and material from China show that, in circumstances with a well organized grass-roots-level network of primary health care services, poisoning episodes can be prevented through dissemination of information of hazards and provision of prevention training courses. Among pesticide manufacturing workers, especially manual packers of organophosphorus insecticides, there is suggestive evidence of subacute poisoning resulting from continuous low-level exposure. Chronic delayed neuropathy has, rarely, been reported. Further study of the cause of subacute poisoning now requires analytical rather than descriptive investigations. There is still no solid documentation of an association of excess human cancer and the use of chlorinated hydrocarbon insecticides. Phenoxyacetic and chlorophenol herbicides recently have been widely studied for causation of soft tissue sarcoma, non-Hodgkin's leukemia, and lymphoma. Although the evidence at present indicates a positive association, discrepancies in findings and resultant controversy require further study. Epidemiological surveys on the harmful effect of DBCP are quite instructive. Investigations in exposed populations verified and extended the observation in animals as infertility and gender ratio change in the next generation. Adverse reproductive effects of a number of pesticides, particularly birth defects resulting from pesticides (other than those already documented for organomercurials), require further study.

An epidemiological study on the effect of N, N'-methylene-bis-(2-amino-1,3,4-thiadiazole) (MATDA) on outcomes of pregnancy.

A retrospective cohort study on the effect of the suspected teratogenic pesticide N, N'-methylene-bis-(2-amino-1,3,4-thiadiazole) (MATDA) on outcomes of pregnancy was conducted. The exposed group (6,173 pregnancies) was composed of childbearing women who, during their gestation, consumed rice harvested from a field where MATDA had been applied. The control I group (10,145) came from an adjacent county where MATDA had never been used; the control II group (3,326) consisted of women who had been pregnant previous to the introduction of this pesticide in the same region as the exposed group. The validity of the survey was verified by comparability and data-checking studies. After adjustment for the calendar year, maternal age, and pregnancy order, no significant differences were found in rates of spontaneous abortion, fetal death and stillbirth, birth defects, as well as in sex ratio and birth weight between the study groups. The same result was found in the comparison of individual categories of malformation. The rates of the birth defects were 23.84, 21.49, and 22.78 per 1,000 live births for the exposed, internal, and external control groups, respectively. No dose-response relationship was revealed. The results were consistent with previous reports and indicated the difference between animal experiments and human exposures. Although MATDA is teratogenic in animals, it is clear that the pesticide does not adversely effect outcomes of pregnancy in humans as currently applied.

Toxicity of dipterex: a field study.

This study summarises historical surveillance data collected from 1977 to 1982 and the results of a field study conducted thereafter (1983-4) in a dipterex packing workshop. The findings suggest that both airborne dipterex and dermal contamination contribute to the inhibition of blood cholinesterase (ChE) and that cases of poisoning in hot seasons can be attributed mainly to dermal absorption. At a level of 0.5 mg/m3, dipterex is shown to lead to a mild but appreciable inhibition of ChE activity. The results also indicate that blood ChE monitoring was sensitive both for long term and short term exposed workers. As a result, the recommendation that the maximum allowable concentration for airborne exposure to dipterex be revised to 0.5 mg/m3, can be regarded at providing only for relative safety.

Clinical observation and comparison of the effectiveness of several oxime cholinesterase reactivators.

After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine aldoxime methylchloride), TMB4 (trimedoxime), and DMO4 (obidoxime, Toxogonin, LüH6)] were compared in clinical trials. All of them proved capable of restoring erythrocyte cholinesterase activity and relieving symptoms and signs of organophosphate insecticide poisoning. Mildly and moderately poisoned patients can be treated by several injections of any one of these drugs alone, but severe cases need the synergistic action of atropine, as well as treatments for two to three consecutive days. Although response to treatment is stronger with TMB4 and DMO4, they are not recommended for routine treatment because of their dangerous adverse side effects.

Prevention of acute parathion and demeton poisoning in farmers around Shanghai.

After the occurrence of poisoning episodes among commune members who handled the insecticides parathion and demeton during the first few years of application in the early 1960s, a series of surveys was conducted and comprehensive regulatory actions were adopted. The surveys showed that the cause of most of the poisoning cases was percutaneous absorption of toxicant as a consequence of skin contamination during careless operating. As a result of a comprehensive program carried out by large numbers of administrators, health workers, and commune members, the incidence of intoxication quickly declined, starting in 1965, to a negligible level and has remained so to the present, even though parathion and demeton use has increased greatly. It is suggested that the experience obtained might be helpful to other areas in the People's Republic of China and in some developing countries.