Histopathological evaluation of tumor necrosis and volume after cyanogenic chemotherapy

PURPOSE: To determine the percentage of tumoral necrosis and volume after cyanogenic chemotherapy. METHODS: Histopathological findings of 20 Swiss mice inoculated subcutaneously in the left abdominal wall with 0.05 ml of cell suspension containing 2.5 x 105 viable cells of the Ehrlich tumor were evaluated. The tumor response to cyanogenic chemotherapy was determined using a system that comprises two inhibition factors of tumor growth by calculating the percentage of necrosis in the tumor tissue and calculation of tumor volume in treated animals relative to that in control animals. The importance of this system has been validated by the correlation between tumor inhibition in the groups treated with the respective percentages of necrosis. RESULTS: While the control group presented an average of 13.48 ± 14.71% necrosis and average tumor volume of 16.18 ± 10.94, the treated group had an average of 42.02 ± 11.58 and 6.8 ± 3.57, respectively. The tumor inhibition was significantly associated with treatment (p=0.0189). The analysis of necrosis percentage showed a significant prognostic importance (p=0.0001). CONCLUSION: It is concluded that the effect of cyanogenic chemotherapy showed strong inhibitory action of tumor growth, as well as an increase in its area of necrosis. .

Impact of sulfur dioxide on hydrogen sulfide/cystathionine-γ-lyase and hydrogen sulfide/mercaptopyruvate sulfurtransferase pathways in the pathogenesis of hypoxic pulmonary hypertension in rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the impact of sulfur dioxide (SO(2)) on hydrogen sulfide (H(2)S)/cystathionine-γ-lyase (CSE) and H(2)S/mercaptopyruvate sulfurtransferase (MPST) pathways in the pathogenesis of hypoxic pulmonary hypertension.</p><p><b>METHODS</b>Thirty-two male Wistar rats were randomly divided into four groups: control group (n = 8), hypoxic group (n = 8), hypoxic + SO(2) group (n = 8) and hypoxic + hydroxamate (HDX) group (n = 8). After 21 days of experiment, the concentration and production of H(2)S in lung tissues were measured respectively for each rat. The protein expression of CSE and MPST in intima and media of small pulmonary arteries in rats was detected with immunohistochemical method.</p><p><b>RESULTS</b>Compared with control group, the mean pulmonary artery pressure (mPAP) in rats of hypoxic group was increased significantly [(33.38 ± 6.32) mm Hg vs. (16.74 ± 3.81) mm Hg, P < 0.01]. Compared with hypoxic group, the mPAP in rats of hypoxic + SO(2) group was decreased significantly [(29.65 ± 2.53) mm Hg vs. (33.38 ± 6.32) mm Hg, P < 0.01]. However, compared with hypoxic group, the mPAP in rats of hypoxic + HDX group was increased significantly [(39.44 ± 6.26) mm Hg vs. (33.38 ± 6.32) mm Hg, P < 0.01]. Compared with control group, the concentration [(2.02 ± 0.43) µmol/g vs. (3.11 ± 0.42) µmol/g, P < 0.01] and production [(19.64 ± 3.48) nmol/(g·min)vs. (28.20 ± 5.95) nmol/(g·min), P < 0.05] of H(2)S were decreased significantly in rats of hypoxic group, respectively. When treated with SO(2), hypoxic rats showed an increased concentration [(2.73 ± 0.20) µmol/g vs. (2.02 ± 0.43) µmol/g, P < 0.01] and production [(26.24 ± 1.92) nmol/(g·min) vs. (19.64 ± 3.48) nmol/(g·min), P < 0.01] of H(2)S in lung tissue compared with those without receiving SO(2) treatment. When treated with HDX, hypoxic rats showed a significant decrease in concentration [(1.64 ± 0.23) µmol/g vs. (2.02 ± 0.43) µmol/g, P < 0.05] and production [(13.94 ± 3.63) nmol/(g·min) vs. (19.64 ± 3.48) nmol/(g·min), P < 0.05] of H(2)S in lung tissue compared with those without receiving HDX treatment. As for the expression of CSE in small pulmonary arteries (SPAs), compared with control group, the expression of CSE in intima [(0.31 ± 0.02) vs. (0.36 ± 0.01), P < 0.01] and media [(0.27 ± 0.01) vs. (0.30 ± 0.01), P < 0.01] in rats of hypoxic group was decreased significantly. While compared with hypoxic group, the expression of CSE in intima [(0.35 ± 0.02) vs. (0.31 ± 0.02), P < 0.01] in SPAs of hypoxic + SO(2) group was increased significantly. With HDX treatment, the expression of CSE in intima [(0.26 ± 0.01) vs. (0.31 ± 0.02), P < 0.01] in SPAs of hypoxic group was lower than that without HDX treatment. As for the expression of MPST in SPAs, compared with hypoxic group, the expression of MPST in media [(0.32 ± 0.02) vs. (0.29 ± 0.01), P < 0.01] in SPAs of hypoxic + SO(2) group was increased significantly.</p><p><b>CONCLUSION</b>SO(2) might upregulate H(2)S/CSE and H(2)S/MPST pathways in pulmonary arteries of hypoxic rats.</p>

Multiple hemodynamic effects of endogenous hydrogen sulfide on central nervous system in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation.</p><p><b>METHODS</b>Ninety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na(+)-K(+)-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student's t test for two groups or analysis of variances (ANOVA) for multiple groups were used to compare the differences of the changes.</p><p><b>RESULTS</b>Intracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta- mercaptopyruvate also increased mean arterial pressure (P < 0.01), whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure (P < 0.01). Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and diastolic pressure; these functions were decreased by hydroxylamine (P < 0.01). Glibenclamide (a K(ATP) channel blocker) blocked the transient hypotensive effect, phentolamine (an alpha-adrenergic receptor blocker) blocked the hypertensive effect, and metoprolol (a selective beta 1 receptor blocker) blocked the positive inoptropic effect of central nervous system hydrogen sulfide. The endogenous digitalis-like factors in plasma were elevated (P < 0.01) after treatment with L-cysteine, association with decreasing Na(+)-K(+)-ATPase activity in cardiac or aortic sarcolemmal vesicles (P < 0.01). Hydroxylamine injection reduced the endogenous digitalis-like factors level in plasma association with increasing Na(+)-K(+)-ATPase activity in cardiac and aortic sarcolemmal vesicles.</p><p><b>CONCLUSION</b>Central nervous system endogenous hydrogen sulfide upregulated mean arterial pressure and cardiac systolic function by activation of sympathetic nerves or release of endogenous digitalis-like factors.</p>

Catalytic and regulatory properties of sulphur metabolizing enzymes in cyanobacterium Synechococcus elongatus PCC 7942.

Synechococcus elongatus PCC 7942 was able to grow with several S sources. The sulphur metabolizing enzymes viz. ATP sulphurylase, cysteine synthase, thiosulphate reductase and L- and D-cysteine desulphydrases were regulated by sulphur sources, particularly by sulphur amino acids and organic sulphate esters. Sulphur starvation reduced ATP sulphurylase and cysteine synthase whereas reduced glutathione appreciated Cys degradation activity. With partially purified enzymes apparent Km values for sulphate, ATP, D- and L-Cys, thiosulphate, sulphide and O-acetyl serine were in a range of 12-50 microM. p-Nitrophenyl sulphate inhibited ATP sulphurylase competitively. Met was a feedback inhibitor of several key enzymes.

Serum rhodanese in goitre and calcific pancreatitis of tropics.

Rhodanese is one of the enzymes concerned in the detoxification of cyanide. Cassava intake and consequent cyanide toxicity are incriminated in the pathogenesis of goitre and calcific pancreatitis of tropics. So we studied the activity of rhodanese in these patients. 14 controls, 13 patients with pancreatitis and 12 with goitre were studied. The median (and range) of rhodanese in these groups were 82 (50-144), 110 (64-180) and 71 (22-160) units respectively. The serum rhodanese was significantly higher (P less than 0.05) in patients with pancreatitis when compared to the other groups. There was no significant difference between the serum rhodanese in patients with goitre and the controls. The presence of adequate amounts of rhodanese indicates that goitre and chronic pancreatitis are not produced by impaired cyanide detoxification.

Pattern of enzyme changes in rabbits administered linamarin or potassium cyanide.

Diseases like tropical ataxic neuropathy and endemic goitre have been reported to have definite correlation with a chronic ingestion of cassava (Manihot esculenta Crantz). The toxicity of cassava has been attributed to its two cyanogenic glycosides, linamarin and lotaustralin. In this study, an attempt has been made to understand the pattern of changes in certain clinically significant enzymes brought about by the chronic administration of sublethal doses of linamarin to rabbits. The profound elevation in rhodanese activity observed in the linamarin and cyanide treated rabbits indicated the attempt of the tissues to detoxify cyanide. That intact linamarin could be hydrolysed in vivo was a significant finding from the study. The mode of toxicity of linamarin was similar to that of cyanide by producing a gradual shift from aerobic to anaerobic metabolism.