Evaluation of the effects of S-methylisothiourea hemisulfate, an inducible nitric oxide synthase inhibitor, on the healing of colonic anastomosis in rats / Avaliação dos efeitos da S-metilisotiouréia, um inibidor da enzima óxido nítrico sintase induzível, na cicatrização de anastomoses colônicas em ratos

PURPOSE: To evaluate the effects of S-methylisothiourea hemisulfate (SMT) on the healing of colonic anastomosis in rats. METHODS: Sixty rats Wistar were distributed into two groups of 30 animals: experimental (E) and control C). The animals of experimental group received intraperitoneal SMT at 50mg/kg/dose every 12 hours for 72 hours. The control group received intraperitoneal saline at the same volume of SMT. The rats were subdivided into subgroups groups of 10 for euthanasia on the third, seventh, and 14th postoperative days (POD). We evaluated clinical and weight evolution, breaking strength and histopathology; also, a blood sample was collected for serum dosage of nitrite/nitrate. RESULTS: There was more vascular neoformation (p=0.006) and granulation (p=0.002) in the E3 group, and more mononuclear infiltrates in the C3 group (p=0.041). There was also more edema in the C14 group (p=0.008). There was no statistically significant difference in breaking strength, nitrite/nitrate dosage, and the remaining histopathological parameters. CONCLUSION: The use of S-methylisothiourea hemisulfate improved the healing of colonic anastomosis in rats on the third postoperative day by accelerating the proliferative stage of healing, but without interfering with the breaking strength of the anastomosis.

OBJETIVO: Avaliar os efeitos do hemissulfato de S-metilisotiouréia (SMT) na cicatrização de anastomoses colônicas em ratos no terceiro, sétimo e 14° dia de pós-operatório (DPO). MÉTODOS: Sessenta ratos Wistar foram distribuídos em dois grupos: experimental (E) e controle (C), com 30 animais cada. No grupo experimental foi administrado SMT 50mg/kg/dose, intraperitoneal a cada 12 horas por 72 horas. O grupo controle recebeu NaCl a 0,9%. Os ratos foram subdivididos em grupos de 10 para eutanásia no terceiro, sétimo e 14° DPO. Avaliou-se a evolução clínica e o peso dos animais, a resistência tênsil e histopatologia da anastomose, e a dosagem de nitrito/nitrato no soro. RESULTADOS: Houve mais neoformação vascular (p=0,006) e de granulação (p=0,002) no grupo E3, e maior infiltração de mononucleares no grupo C3 (p=0,041). Houve também mais edema no grupo C14 (p=0,008). Não houve diferença estatisticamente significativa na resistência tênsil, a dosagem de nitrito / nitrato, e os restantes parâmetros histopatológicos. CONCLUSÃO: A utilização do hemissulfato de S-metilisotiouréia acelerou a cicatrização das anastomoses colônicas, a melhoria ocorreu no terceiro DPO: verificou-se que a fase proliferativa da cicatrização foi acelerada. Não houve interferência na resistência tênsil das anastomoses.

Animal experimental study of intra-articular injection of S-methylisothiourea for treatment of temporomandibular joint osteoarthrosis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of S-methylisothiourea (SMT) for treatment of temporomandibular joint osteoarthrosis (TMJOA) of goats.</p><p><b>METHODS</b>Nine purebred black goats were randomly devided into three groups: Normal control group, control group and experimental group. The upper compartments of both temporomandibular joint of the goats in control group and experimental group were injected with collagenase only once to induce osteoarthrosis. Normal control group received no treatment. The upper compartments of both TMJ were injected with 0.5 mL of normal saline, and experimental group, the upper compartments of both TMJ were injected with 0.5 mL of SMT. The TMJ of goats was examined with scanning electron microscopy and microscopy after sacrificed.</p><p><b>RESULTS</b>Examined in light microscopy and scanning electron microscopy, normal control group showed normal performance, the control group showed severe osteoarthrotic changes in the temporal surface, disk and condyle, while the experimental group showed improvement of different degree.</p><p><b>CONCLUSION</b>On the basis of 3-month following-up study, repeated intra-articular injection of SMT may play a role in inhibiting TMJOA progression.</p>

Influence of induced nitric oxide synthase expression on apoptosis of thymocyte in burn rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the influence of induced nitric oxide synthase (iNOS) expression on apoptosis of thymocyte in burn rats, and to explore the relationship between NO and pathological lesion of the thymus gland in burn rats.</p><p><b>METHODS</b>Fifty-six male Wistar rats were enrolled in the study and randomized into control( C, n = 8,without treatment) , burn ( B, n = 24) , and S-methylisothiourea( SMT, n = 24) groups. Equal amount of isotonic saline solution and SMT(7. 5 mg/kg) were respectively intravenously infused into the rats in B and SMT groups after being inflicted with 30% TBSA full-thickness burns. The weight of thymus gland in each group were weighed, and thymocyte apoptosis and iNOS expression were determined with TUNEL method and immunohistochemistry, respectively at 6,24,72 postburn hours( PBH) , with 8 rats at each time-point. The number of apoptotic cells and the density of iNOS positive cells in thymus was measured by stereological method.</p><p><b>RESULTS</b>The weight of thymus in B group at 24 and 72 PBH [ (153+/- 14) , (91+/-22) mg] were obviously heavier than those in C group, but much lighter than those in SMT group ( P < 0.01). A few apoptotic cells and iNOS positive cells were observed in cortex and medulla of thymus in C group, while they were observed in B group at 6 PBH, and the number of cells began to increase at 24 PBH, distributing in medulla,parenchyma, the boundary of cortex, and medulla under capsule. The iNOS positive cells in B group at 24 PBH were distributed around the interlobular septum. A large number of cortical cells with brown staining were observed in B group at 72 PBH, and the number of iNOS positive cells also increased, with scattered distribution and clear cell boundary. Fewer positive cells with uneven distribution, no iNOS positive cells, and few apoptotic foci were observed in SMT group after burns. The density of apoptotic cells in B group at 24 and 72 PBH was (2. 428 +/-0. 728) x 10(-5)/microm(3) and (5. 586 +/- 1.233) x 10(-5)/microm(3), respectively, which was obviously higher than that in C and SMT group. The density of iNOS positive cells in B group was increased in a time-dependent manner( P <0. 05).</p><p><b>CONCLUSION</b>The apoptotic rate of thymocyte in severely burn rats increases early after burns. The up-regulation of iNOS expression in thymus can promote apoptosis of thymocytes, while SMT can partially ameliorate this phenomenon.</p>

Effect of nitric oxide synthase inhibitor on proteoglycan metabolism in repaired articular cartilage in rabbits / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the effect of nitric oxide synthase inhibitor, S-methyl thiocarbamate (SMT), on proteoglycan metabolism in repaired articular cartilage in rabbits.</p><p><b>METHODS</b>Twenty-four male New Zealand white rabbits, aged 8 months and weighing 2.5 kg+/-0.2 kg, were used in this study. Cartilage defects in full thickness were created on the intercondylar articular surface of bilateral femurs of all the rabbits. Then the rabbits were randomly divided into 3 groups (n=8 in each group). The defects in one group were filled with fibrin glue impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2, BMP group), in one group with fibrin glue impregnated with rhBMP-2 and hypodermic injection with SMT (SMT group) and in the other group with nothing (control group). All the animals were killed at one year postoperatively. The tissue sections were stained with safranine O-fast green and analyzed by Quantiment 500 system to determine the content of glycosaminoglycan through measuring the percentage of safranine O-stained area, the thickness of cartilages and the mean gray scale (average stain intensity). Radiolabelled sodium sulphate (Na(2)(35)SO(4)) was used to assess the proteoglycan synthesis.</p><p><b>RESULTS</b>At one year postoperatively, the percentage of safranine O-stained area, the mean gray scale and the cartilage thickness of the repaired tissues in SMT group were significantly higher than those of BMP group (P<0.01) and the control group (P<0.05). Result of incorporation of Na(2)(35)SO(4) showed that the proteoglycan synthesis in SMT group was higher than those of BMP group and the control group (P<0.01).</p><p><b>CONCLUSIONS</b>SMT, a nitric oxide synthase inhibitor, can significantly increase the content of glycosaminoglycan and proteoglycan synthesis, and computer-based image analysis is a reliable method for evaluating proteoglycan metabolism.</p>

Drogas, inibidores y otras historias. De la quimioterapia a la toxicologia nutricional / Drugs, inhibitors and other stories. From cancer chemotherapy to nutritional toxicology

La designación como ponente de la XVIII Conferencia Annual "Karl Gaede", instituída por la Asociación Venezolana de Bioquímica y Biología Molecular, me brindó la oportunidad para emprender un viaje retrospectivo a través de algunos aspectos de la actividad de investigación realizada a lo largo de 25 años de dedicación al oficio de la bioquímica. Dicho derrotero se desplaza desde la quimioterapia del cáncer a la toxicología nutricional, siguiendo el elusivo hilo conductor del metabolismo, realidad subyacente bajo todo proceso biológico. El presente ensayo resume experiencias derivadas del abordaje de problemas metabólicos a través del uso de drogas, inhibidores y estimuladores que actúan sobre pasos enzimáticos específicos. Con estas herramientas del artesano metabólico es posible descorrer los velos que recubren al hilo conductor, para exponer las peculiaridades que lo caracterizan en el entorno de un problema particular y las semejanzas con los de otros que le dan continuidad en el amplio espectro del universo que nos atañe.