Expression of Metallothionein after Administration of Aspirin, Vitamin C or Zinc Supplement in the DMH Induced Colon Carcinoma in Rat

Background: Chemoprevention refers to the use of specificnatural or synthetic chemical agents to suppress the development and progression to carcinoma. The purpose of this study was to assess the effect of aspirin, vitamin C or zinc on the metallothionein (MT) mRNA gene expression as well as MT protein content byimmunohistochemistry andradioimmunoassay (RIA) in 1, 2-dimethyl hydrazine (DMH) induced cancerous colonic tissuein rats. Methods: Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) group 3 (zinc), each of which was further sub divided into two groups and given subcutaneous injections of DMH (30 mg/kg body weight) twice a week for 3 months and sacrificed at either 4 months (A-precancer model) or at 6 months (B-cancer model).The control groups were administered 0.5 ml saline subcutaneously. All the 3 groups were simultaneouslyadministered aspirin, vitamin Cor zinc supplement respectively from the beginning till the end of the study. Results: It was observed that rats co-treated with aspirin, vitamin C or zinc resulted in a significant increase in the colonic MT mRNA expression in the precancer and cancer model as compared to the saline only controls. MT protein expression showed a 60%, 64% and 78% immunopositivity in the co-treated groups respectively.The mean MT content in the precancer and the cancer model was restored to near normal levels in all the three co-treated groups. Conclusion: These results suggest that co-administration of aspirin, vitamin C or zinc resulted in a significant increase in MT mRNA gene expression, MT protein expression and MT protein content which could possibly be one of the reasons for a chemo protective effect against progression to colonic cancer in a chemically induced DMH model in rat.Zinc supplement had a greater effect on metallothionein expression than aspirin or vitamin C.

Expression of metallothionein in dimethylhydrazine-induced colonic precancerous and cancerous model in rat.

AIM: Metallothionein (MT) is a small protein with a high affinity for divalent heavy metals and has a function in zinc homeostasis. The purpose of this study was to assess the MT mRNA gene expression as well as the MT protein content by immunohistochemistry and radioimmunoassay (RIA) in 1,2-dimethylhydrazine (DMH)-induced precancerous and cancerous colonic tissue in rats. MATERIALS AND METHODS: Six-week-old rats were given subcutaneous injections of DMH twice a week for 3 months and sacrificed at 4 months (precancerous model) and 6 months (cancerous model). We determined MT mRNA expression by reverse transcription polymerase chain reaction and MT protein content by both immunohistochemical expression and cadmium-109 RIA. RESULTS: MT mRNA expression in the large intestine showed statistically significant decrease in the precancerous (P < 0.01) and the cancerous (P < 0.001) model as compared with controls. Immunohistochemical expression of MT showed statistically significant decrease (P < 0.05) in the colonic cancerous tissue. MT content in the large intestine showed statistically significant decrease in precancerous (P < 0.005) and cancerous (P < 0.001) model as compared with controls. CONCLUSION: This study suggests that a decrease in the colonic MT mRNA expression, MT protein expression, and content in DMH-induced colonic cancer model is associated with the development of preneoplastic lesions and further progression to carcinoma in the colon results in a greater reduction in the levels of each of these parameters.

Estimation of Monocrotophos renal elimination half-life in humans.

INTRODUCTION: Monocrotophos, implicated in about 1/4th of organophosphate poisonings in our centre, is associated with the highest mortality (24%). Yet data on its pharmacokinetics in humans is limited. We estimated the renal elimination half-life of monocrotophos. PATIENTS AND METHODS: Consecutive patients presenting with monocrotophos overdose over a 2-month period who had normal renal function were recruited. Monocrotophos in plasma and urine were quantitated by high-performance liquid chromatography. Urine was obtained from catheterised samples at 0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 h. Plasma specimens were collected at the time of admission, and at the midpoint of the urine sample collections at 1, 3, 5, 7, 10, 15 and 21 h. Renal elimination half-life was calculated from the cumulative amount excreted in the urine. RESULTS: The cohort of 5 male patients, aged 35.8 ± 2.94 years, presented with typical organophosphate (cholinergic) toxidrome following intentional monocrotophos overdose. All patients required mechanical ventilation; one patient died. Plasma data was available from 5 patients and urine data from 3 patients. The median renal elimination half-life was 3.3 (range: 1.9-5.0 h). Plasma monocrotophos values, as natural log, fell in a linear fashion up to around 10 h after admission. After the 10-hour period, there was a secondary rise in values in all the 3 patients in whom sampling was continued after 10 h. CONCLUSION: A renal elimination half-life of 3.3 h for monocrotophos is consistent with a water-soluble compound which is rapidly cleared from the plasma. The secondary rise in plasma monocrotophos values suggests possible re-distribution. Determining the elimination profile of this compound will help develop better strategies for treatment.

Protective role of aspirin, vitamin C, and zinc and their effects on zinc status in the DMH-induced colon carcinoma model.

Chemoprotection refers to the use of specific natural or synthetic chemical agents to suppress or prevent the progression to cancer. The purpose of this study is to assess the protective effect of aspirin, vitamin C or zinc in a dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the effect of these supplements on changes associated with colonic zinc status. Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) and group 3 (zinc), each being subdivided into two groups and given subcutaneous injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4 months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were simultaneously given aspirin, vitamin C, or zinc supplement respectively from the beginning till the end of the study. It was observed that 87.5% of rats co-treated with aspirin or vitamin C showed normal colonic histology, along with a significant decrease in colonic tissue zinc at both time points. Rats co-treated with zinc showed 100% reduction in tumor incidence with no significant change in colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide dismutase) and alkaline phosphatase activity showed no significant changes in all 3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given separately, exert a chemoprotective effect against chemically induced DMH colonic preneoplastic progression and colonic carcinogenesis in rats. The inhibitory effects are associated with maintaining the colonic tissue zinc levels and zinc enzymes at near normal without significant changes.

Predictors of osteodystrophy in patients with chronic nonalcoholic pancreatitis with or without diabetes.

OBJECTIVE: To study bone mineral content (BMC), bone mineral density (BMD), vitamin D status, and bone mineral variables in patients with chronic nonalcoholic pancreatitis and to determine the relationship between pancreatic dysfunction and these variables. METHODS: Thirty-one eligible nonalcoholic men with proven chronic pancreatitis and 35 male control subjects were studied. Biochemical data, variables of malabsorption, and BMD of the lumbar spine were evaluated. RESULTS: In patients with chronic pancreatitis, the mean body mass index (BMI) was 18.46 kg/m² and the median 25-hydroxyvitamin D value was 15.5 (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35, 9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients with chronic pancreatitis and steatorrhea. There was no significant correlation between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with steatorrhea had a significantly lower BMC than did those without steatorrhea, and this difference could not be accounted for by differences in BMI, presence of diabetes, or hypovitaminosis D. CONCLUSION: Pancreatic osteodystrophy is a novel entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with chronic pancreatitis. The inverse correlation between stool fat and BMC in patients with chronic pancreatitis, the strong positive correlation between BMI and BMC, and the lack of difference in BMC between subjects with vitamin D sufficiency and those with vitamin D deficiency suggest that long-standing malabsorption with attendant chronic undernutrition is the major factor contributing to the changes in BMC.

Electrolytes assessed by point-of-care testing - Are the values comparable with results obtained from the central laboratory?

BACKGROUND AND AIMS: When dealing with very sick patients, the speed and accuracy of tests to detect metabolic derangements is very important. We evaluated if there was agreement between whole blood electrolytes measured by a point-of-care device and serum electrolytes measured using indirect ion-selective electrodes. MATERIALS AND METHODS: In this prospective study, electrolytes were analyzed in 44 paired samples drawn from critically ill patients. Whole blood electrolytes were analyzed using a point-of-care blood gas analyzer and serum electrolytes were analyzed in the central laboratory on samples transported through a rapid transit pneumatic system. Agreement was summarized by the mean difference with 95% limits of agreement (LOA) and Lin's concordance correlation (p(c)). RESULTS: There was a significant difference in the mean (±standard deviation) sodium value between whole blood and serum samples (135.8 ± 5.7 mmol/L vs. 139.9 ± 5.4 mmol/L, P < 0.001), with the agreement being modest (p(c) = 0.71; mean difference -4.0; 95% LOA -8.78 to 0.65). Although the agreement between whole blood and serum potassium was good (p(c) = 0.96), and the average difference small (-0.3; 95% LOA -0.72 to 0.13), individual differences were clinically significant, particularly at lower potassium values. For potassium values <3.0 mmol/L, the concordance was low (p(c) = 0.53) and the LOA was wide (1.0 to -0.13). The concordance for potassium was good (p(c) = 0.96) for values ≥3.0 (mean difference -0.2; 95% LOA -0.48 to 0.06). CONCLUSIONS: Clinicians should be aware of the difference between whole blood and serum electrolytes, particularly when urgent samples are tested at point of care and routine follow-up electrolytes are sent to the central laboratory. A correction factor needs to be determined at each center.

Agreement between paired blood gas values in samples transported either by a pneumatic system or by human courier.

BACKGROUND: Rapid accurate assessment of metabolic derangements is crucial in the critically ill. We evaluated if arterial blood gas (ABG) samples transported through a pneumatic tube system (PTS) agreed with values transported by a human courier. METHODS: In this prospective study of 50-paired ABG samples, the couriered reference ABG was compared with those transported by PTS. Agreement was summarised by the mean difference with 95% limits of agreement (LOA) and Lin's concordance correlation (pc). RESULTS: The mean (±SD) time from sampling to analysis was 35.7±23.2 (courier) and 38.6±22.1 (PTS) minutes. Agreement was good between courier and PTS for pH, PaCO(2), bicarbonate, oxygen saturation and PaO(2) values (pc>0.97). Although the mean difference in PaO(2) values between PTS and courier was small (-0.9 mm Hg) and the agreement was good, individual differences were clinically significant (95% LOA -40.8 to 39.0). For PaO(2) <160 mm Hg, analysis of PTS samples yielded erroneously high PaO(2) values and vice versa for PaO(2)>160 mm Hg compared to manual courier. This suggested exaggerated oxygen movement between the blood sample and air in the PTS. CONCLUSIONS: In this study, analysis of samples transported through the PTS resulted in clinically unacceptable PaO(2) values. Delay in transport and analysis of ABG samples should be avoided and samples transported manually if they cannot be assessed on-site.