Valproic acid and bladder healing: an experimental study in rats.

PURPOSE: to recognize the effects of valproic acid (VPA), an epigenetic drug, on the bladder healing process, in rats. METHOD: twenty male Wistar rats were divided in two groups: experimental (A), treated with VPA (150mg/Kg/day), and control (B) with 0.9% sodium chloridrate. Healing was analyzed on the third and seventh days, evaluating the inflammatory reaction, collagen synthesis and angiogenesis. RESULTS: inflammatory reaction on the third day was minimal and acute in both groups. On the seventh day, it was subacute in both groups, moderate intensity in group A and minimal in group B (p=0.0476). Collagen III intensity, marked by immunohistochemistry, was similar in both groups. Collagen I intensity on the third day was similar in both groups, but on the seventh day it was higher in experimental than control (p=0.0476). Collagen evaluation by picrosiriusred allowed to verify that the presence of collagen III was similar in both groups (p=0.3312) on the third day, and it was higher in control on the seventh day (p=0.0015). Collagen I showed similarity on the third day (p=0.3100), and it was higher in control on the seventh day (p=0.0015). Vessel marked with anti-SMA counting showed fewer vessels on the third (p=0.0034) and seventh day (p=0.0087) in experimental group. The lower intensity of angiogenesis was confirmed with anti-CD34, on the third day (p=0,0006) and on the seventh day (p=0,0072). CONCLUSION: VPA determined alterations in the bladder healing process, in rats, with lower collagen density and less angiogenic activity, but without compromising the integrity of the organ.

The effects of valproic acid on skin healing: experimental study in rats.

PURPOSE: To recognize the effects of valproic acid (VPA), an epigenetic drug, on the skin healing process. METHODS: Sixty male Wistar rats were divided into two groups: the experiment treated with VPA (100 mg/kg/day); and the control, with 0.9% sodium chloride by gavage. Skin healing was studied in three moments (the third, the seventh, and the 14th day), evaluating the parameters: inflammatory reaction and its intensity (anti-LCA), angiogenesis (anti-CD34), collagen I and III (anti-collagen I, anti-collagen III and Picrosirius-red F3BA) and myofibroblasts (anti-alpha-AMS). RESULTS: The inflammatory reaction was acute or sub-acute in both groups on the third day. On the seventh and the 14th day, chronic predominated in the control (p=0.006), and sub-acute in the experiment (p=0.020). There was a greater number of leukocytes in the group treated only on the third day (p=0.036). The number of vessels was lower in the treated group at the three times (p3=0.002, p7<0.001, and p14=0.027). Myofibroblasts were rare in the third day and moderate quantity in the remaining periods. Collagen I density was higher in the control at the three times (p<0.001) and collagen III in the treated group (p<0.001). CONCLUSIONS: VPA led to a more intense inflammatory reaction, decreased angiogenesis and collagen deposition, especially type I collagen.

Valproic acid and bladder healing: an experimental study in rats / Ácido valpróico e cicatrização em bexiga: estudo experimental em ratos

ABSTRACT Purpose: to recognize the effects of valproic acid (VPA), an epigenetic drug, on the bladder healing process, in rats. Method: twenty male Wistar rats were divided in two groups: experimental (A), treated with VPA (150mg/Kg/day), and control (B) with 0.9% sodium chloridrate. Healing was analyzed on the third and seventh days, evaluating the inflammatory reaction, collagen synthesis and angiogenesis. Results: inflammatory reaction on the third day was minimal and acute in both groups. On the seventh day, it was subacute in both groups, moderate intensity in group A and minimal in group B (p=0.0476). Collagen III intensity, marked by immunohistochemistry, was similar in both groups. Collagen I intensity on the third day was similar in both groups, but on the seventh day it was higher in experimental than control (p=0.0476). Collagen evaluation by picrosiriusred allowed to verify that the presence of collagen III was similar in both groups (p=0.3312) on the third day, and it was higher in control on the seventh day (p=0.0015). Collagen I showed similarity on the third day (p=0.3100), and it was higher in control on the seventh day (p=0.0015). Vessel marked with anti-SMA counting showed fewer vessels on the third (p=0.0034) and seventh day (p=0.0087) in experimental group. The lower intensity of angiogenesis was confirmed with anti-CD34, on the third day (p=0,0006) and on the seventh day (p=0,0072). Conclusion: VPA determined alterations in the bladder healing process, in rats, with lower collagen density and less angiogenic activity, but without compromising the integrity of the organ.

RESUMO Objetivo: reconhecer os efeitos do ácido valpróico (VPA), uma droga epigenética, no processo de cicatrização da bexiga, em ratos. Método: vinte ratos Wistar machos foram divididos em dois grupos: experimental (A), utilizando VPA (150mg/Kg/dia), e controle (B), tratados com cloreto de sódio 0,9% por gavagem. A cicatrização da bexiga foi analisada no terceiro e sétimo dia, estudando-se a reação inflamatória, síntese de colágeno, reepitelização e angiogênese. Resultados: a reação inflamatória no terceiro dia foi mínima e aguda em ambos os grupos. No sétimo dia, foi subaguda em ambos os grupos com intensidade moderada no grupo A e mínima no grupo B (p=0,0476). A intensidade do colágeno III, marcada pela imuno-histoquímica, foi semelhante nos dois grupos, nos dois tempos estudados. A intensidade de colágeno I no terceiro dia foi semelhante nos dois grupos, e maior no sétimo dia no grupo experimental (p=0,0476). A avaliação do colágeno pelo picrosiriusred mostrou que a presença de colágeno III foi semelhante em ambos os grupos (p=0,3312) no terceiro dia, e maior no controle no sétimo dia (p=0,0015). O colágeno I foi semelhante no terceiro dia (p=0,3100), e maior no controle no sétimo dia (p=0,0015). A contagem de vasos marcados pelo anti-SMA mostrou menos vasos no terceiro (p=0,0034) e sétimo dia (p=0,0087) no grupo experimental, confirmado pelo anti-CD34, no terceiro (p=00006) e no sétimo dia (p=0,0072). Conclusão: o VPA determinou alterações no processo de cicatrização da bexiga, em ratos, com menor densidade de colágeno e menor atividade angiogênica, mas sem comprometer a integridade do órgão.

Histological evaluation of the effect of low-frequency electric stimulation on healing Achilles tendons in rats.

PURPOSE: Histologically evaluate the effects of low frequency electrical stimulation in the treatment of Achilles tendon injuries in rats. METHODS: Thirty-four rats underwent Achilles tendon tenotomy and tenorrhaphy. They were randomly allocated in two groups. Half of the sample constituted the experiment group, whose lesions were stimulated with 2 Hz, nonpolarized current and 1 mA, for 14 days. The other animals formed the control group. They were evaluated at 2, 4 and 6 weeks. The histological study was carried out, the collagen density and the wound maturity index were measured. RESULTS: The healing score was higher in the group stimulated at the 6th week (p = 0.018). The density collagen 1 was higher in the group treated at the three times (p = 0.004) and that collagen 3 was higher in the group treated at 6 weeks (p = 0.004). Together, collagen 1 and 3 were higher in the group stimulated at 4 and 6 weeks (p = 0.009, p = 0.004). The maturity index was higher in this group at the three moments (p = 0.017 p = 0.004 and p = 0.009). CONCLUSION: Low frequency electric stimulation improved healing and increased the quantity of collagen.

Tensiometric evaluation of the effect of lowfrequency electric stimulation on healing Achilles tendons in rats.

PURPOSE: To evaluate the effects of low-frequency electric stimulation on biomechanics following surgical treatment of the Achilles tendon in rats. METHODS: Forty-two rats were divided into two groups. One was given electric stimulation and the other was not. All were submitted to Achilles tenotomy and tenorrhaphy performed with a modified Kessler stitch. The experiment group underwent electric stimulation with 2 Hz, a nonpolarized current of 1 mA intensity for 14 days. The animals were euthanized at 2, 4 and 6 weeks for the biomechanical study. RESULTS: The work performed, that is, the tendon's capacity to absorb energy until rupture, was greater in the electrically stimulated group in the 2nd (p = 0.032) and in the 6th week (p = 0.010). The maximum tension, which is the capacity to support a load, was higher in the treated group in the 2nd (p = 0.030) and the 6th week (p = 024). These results indicate greater resistance of the electrically stimulated tendons. An analysis of the elastic module showed no differences. CONCLUSION: Low-frequency electric stimulation increased the resistance of the tendons at 2 and 6 weeks of evolution in rats.

Comparative study of fibrosis induced by Marlex®, Parietex Composite®, Vicryl® and Ultrapro® meshes1.

PURPOSE: To evaluate the fibrosis induced by four different meshes: Marlex®, Parietex Composite®, Vicryl® and Ultrapro®. METHODS: Histological cutouts of abdominal wall were analyzed with polarized light 28 days after the meshes implants and colorized by picrosirius to identify the intensity of collagen types I and III, and their maturation index. RESULTS: When the four groups were compared, the total collagen area analyzed was bigger in groups A and D, with no difference between them. The collagen type I density was bigger in group A, with an average of 9.62 ± 1.0, and smaller in group C, with an average of 3.86 ± 0.59. The collagen type III density was similar in groups A, B and C, and bigger in group D. The collagen maturation index was different in each of the four groups, bigger in group A with 0.87, group B with 0.66, group D with 0.57 and group C with 0.33 (p = 0.0000). CONCLUSION: The most prominent fibrosis promotion in the given meshes was found on Marlex® (polypropylene mesh) and the Parietex Composite® (non-biodegradable polyester); the collagen maturation index was higher in the Marlex® mesh, followed by Ultrapro®, Parietex Composite® and Vicryl® meshes.

Comparative study of fibrosis induced by Marlex®, Parietex Composite®, Vicryl® and Ultrapro® meshes1

Abstract Purpose: To evaluate the fibrosis induced by four different meshes: Marlex®, Parietex Composite®, Vicryl® and Ultrapro®. Methods: Histological cutouts of abdominal wall were analyzed with polarized light 28 days after the meshes implants and colorized by picrosirius to identify the intensity of collagen types I and III, and their maturation index. Results: When the four groups were compared, the total collagen area analyzed was bigger in groups A and D, with no difference between them. The collagen type I density was bigger in group A, with an average of 9.62 ± 1.0, and smaller in group C, with an average of 3.86 ± 0.59. The collagen type III density was similar in groups A, B and C, and bigger in group D. The collagen maturation index was different in each of the four groups, bigger in group A with 0.87, group B with 0.66, group D with 0.57 and group C with 0.33 (p = 0.0000). Conclusion: The most prominent fibrosis promotion in the given meshes was found on Marlex® (polypropylene mesh) and the Parietex Composite® (non-biodegradable polyester); the collagen maturation index was higher in the Marlex® mesh, followed by Ultrapro®, Parietex Composite® and Vicryl® meshes.

Influência do envelhecimento na qualidade da pele de mulheres brancas: o papel do colágeno, da densidade de material elástico e da vascularização / Influence of aging on the skin quality of white-skinned women: the role of collagen, elastic material density, and vascularization

INTRODUÇÃO: O objetivo deste estudo é avaliar a influência do envelhecimento na qualidade da pele de mulheres brancas, analisando o colágeno, as fibras elásticas e a vascularização. MÉTODO: Foi realizada análise histológica e morfométrica de 218 retalhos pré-auriculares de mulheres brancas, que se submeteram a cirurgia estética facial. Foram utilizados o imunomarcador AntiCD 34, que evidencia os vasos sanguíneos, a coloração de Weigert, para visibilização das fibras elásticas, e a coloração de Picrosirius Ultrared, para analisar e quantificar os colágenos I, III e total. Os dados foram analisados de acordo com a faixa etárias das doadoras: < 40 anos, 40 anos a 49 anos, 50 anos a 59 anos, 60 anos a 69 anos, e > 70 anos. RESULTADOS: Foi observada fragmentação e desorganização das fibras de colágeno, especialmente acima de 60 anos. Não houve diferenças significantes entre a idade e a espessura da derme e da epiderme, porém foi identificada relação com as porcentagens de colágeno I, III e total (P < 0,001). Houve aumento da densidade de fibras elásticas com a progressão da idade (P < 0,001). Comparando-se as peles das pacientes de faixas etárias vizinhas, com diferença de uma década entre elas, não houve diferença significativa na quantidade de material elástico dessas peles; porém, ao se comparar aquelas com diferença de 2 ou mais décadas nas faixas etárias, o aumento foi significante (P < 0,05). A diferença do número de vasos não foi significante (P = 0,112). CONCLUSÕES: O envelhecimento promoveu redução do colágeno, degradação e fragmentação das fibras, e aumento da densidade de material elástico desorganizado, e não influenciou no número de vasos sanguíneos da derme.

BACKGROUND: In the present study, we aimed to evaluate the influence of aging on the skin quality of white-skinned women by assessing collagen levels, elastic material density, and vascularization. METHODS: Histological and morphometric analyses were performed on 218 preauricular skin fragments from white-skinned women who underwent facial cosmetic surgery. Anti-CD34 was used to identify the blood vessels, Weigert's staining was used to visualize elastic fibers, and Picro-sirius Ultra Red staining was employed for analyzing and quantifying the expression of type I, III, and total collagen. Data were analyzed according to the following donor age groups: < 40, 40-49, 50-59, 60-69, and > 70 years. RESULTS: Fragmentation and disorganization of collagen fibers were observed in certain samples, particularly in samples from patients aged > 60 years. Significant differences between age and the thickness of the dermis and epidermis were not detected. However, a relationship was identified between age and the percentages of type I, III, and total collagen, and an increase of elastic fibers density was associated with age progression (P < 0.001). The comparison of the skin of patients with a decade difference in age did not reveal a significant difference in the elastic material quality; however, when the age difference was of 2 decades or more, there was a significant difference in elastic fibers (P < 0.05). The difference in the number of blood vessels between the groups was not significant (P = 0.112). CONCLUSIONS: Aging promoted collagen reduction, fiber degradation and fragmentation, and increased disorganized elastic material density; however, it did not affect the number of dermal blood vessels.

Obesity and abdominal wound healing in rats.

INTRODUCTION: Treatment for obesity essentially has to do with weight loss, which can be achieved through surgical procedures. Despite the considerable rise in the number of such procedures, the relationship between obesity and the healing process has not been totally clarified. PURPOSE: To investigate abdominal wound healing in obese Wistar rats on the seventh and fourteenth days following a laparotomy. METHODS: Thirty-six Wistar rats were randomly distributed into two groups, the control and experiment group. The control group were fed on either a standard diet for the species and the experiment group were put on a high calorie diet. After 116 days, all the animals were submitted to a laparotomy followed by laparorrhaphy. After euthanasia on the seventh or fourteenth day, fragments of the abdominal wound containing the scar were submitted to histopathological and tensiometric analysis. RESULTS: The average weight of the animals from the experiment group was higher than that of the control group (p<0.001). The difference in the resistance of the cutaneous scars was not significant. The aponeurotic scars were more resistant in the control group after seven days (p=0.011) and fourteen days (p=0.040). There was no difference in terms of intensity of the inflammatory reaction and the collagen density was similar in both groups. CONCLUSION: In rats, obesity lowered the resistance of the aponeurotic scars but not the skin scars. It did not interfere with the delayed inflammatory response and the collagen density.

Obesity and abdominal wound healing in rats / Obesidade e cicatrização da parede abdominal em ratos

INTRODUCTION: Treatment for obesity essentially has to do with weight loss, which can be achieved through surgical procedures. Despite the considerable rise in the number of such procedures, the relationship between obesity and the healing process has not been totally clarified. PURPOSE: To investigate abdominal wound healing in obese Wistar rats on the seventh and fourteenth days following a laparotomy. METHODS: Thirty-six Wistar rats were randomly distributed into two groups, the control and experiment group. The control group were fed on either a standard diet for the species and the experiment group were put on a high calorie diet. After 116 days, all the animals were submitted to a laparotomy followed by laparorrhaphy. After euthanasia on the seventh or fourteenth day, fragments of the abdominal wound containing the scar were submitted to histopathological and tensiometric analysis. RESULTS: The average weight of the animals from the experiment group was higher than that of the control group (p<0.001). The difference in the resistance of the cutaneous scars was not significant. The aponeurotic scars were more resistant in the control group after seven days (p=0.011) and fourteen days (p=0.040). There was no difference in terms of intensity of the inflammatory reaction and the collagen density was similar in both groups. CONCLUSION: In rats, obesity lowered the resistance of the aponeurotic scars but not the skin scars. It did not interfere with the delayed inflammatory response and the collagen density.

INTRODUÇÃO: O tratamento da obesidade é baseado essencialmente na perda de peso, e isto pode ser conseguido por meio de procedimentos cirúrgicos. Apesar do grande aumento no número destes procedimentos, a relação entre obesidade e o processo de cicatrização ainda não está totalmente elucidada. OBJETIVO: Investigar a cicatrização da parede abdominal de ratos Wistar obesos, sete e 14 dias após laparotomia. MÉTODOS: Ratos Wistar, em número de 36 foram alocados em dois grupos, controle e experimento. Os do grupo controle receberam dieta padrão para a espécie e os do experimento dieta hipercalórica. Depois de 116 dias, todos os animais foram submetidos à laparotomia seguida de laparorrafia. Após a eutanásia com sete ou 14 dias, fragmentos da parede abdominal contendo a cicatriz receberam análise histopatológica e tensiométrica. RESULTADOS: O peso médio dos animais do grupo experimento foi maior do que o do grupo controle (p<0,001). A diferença da resistência das cicatrizes cutâneas não foi significante. As cicatrizes aponeuróticas foram mais resistentes no grupo controle aos sete dias (p=0,011) e aos 14 dias (p=0,040). Não houve diferença quanto à intensidade da reação inflamatória e a densidade de colágeno foi semelhante nos dois grupos. CONCLUSÃO: Em ratos, a obesidade diminuiu a resistência das cicatrizes aponeuróticas, mas não a das cicatrizes da pele. Não interferiu na reação inflamatória tardia e nem na densidade do colágeno.

The influence of nicotine on the population of fibroblasts in cutaneous scars in rats.

PURPOSE: To study the collagen density and the population of fibroblasts in cutaneous injuries in rats under the influence of nicotine. METHODS: The scars of abdominal wounds in rats were analyzed. 2 mg/kg/d of nicotine was administered to the animals in the experiment group and the solution used as a vehicle for the animals in the control group. Treatment was begun seven days prior to surgery and maintained for seven or fourteen days following surgery. The removed scars were prepared for histopathological study. Histological cuts were stained by Sirius Supra red F3BA for collagen analysis and submitted to the examination using the immunohistochemical technique, which enabled us to recognize the population of fibroblasts. RESULTS: No significant difference was found in type I collagen density after seven days (p=0.912), nor after fourteen days (p=0.211). The control group had more type III collagen after seven days (p=0.004), but after fourteen days there was no significant difference (p=0,720). The total quantification of collagen, although higher in the control group, was not significantly so at any time during the study (p=0.103 after seven days and p=0.549 after fourteen days). The average of fibroblasts per field was lower after seven days (p=0.0001) and after fourteen days (p=0.0000). CONCLUSION: Under the conditions of this experiment, nicotine reduced the fibroblast population without modifying collagen density significantly.

The influence of nicotine on the population of fibroblasts in cutaneous scars in rats / A influência da nicotina na população de fibroblastos em cicatrizes cutâneas de ratos

PURPOSE: To study the collagen density and the population of fibroblasts in cutaneous injuries in rats under the influence of nicotine. METHODS: The scars of abdominal wounds in rats were analyzed. 2 mg/kg/d of nicotine was administered to the animals in the experiment group and the solution used as a vehicle for the animals in the control group. Treatment was begun seven days prior to surgery and maintained for seven or fourteen days following surgery. The removed scars were prepared for histopathological study. Histological cuts were stained by Sirius Supra red F3BA for collagen analysis and submitted to the examination using the immunohistochemical technique, which enabled us to recognize the population of fibroblasts. RESULTS: No significant difference was found in type I collagen density after seven days (p=0.912), nor after fourteen days (p=0.211). The control group had more type III collagen after seven days (p=0.004), but after fourteen days there was no significant difference (p=0,720). The total quantification of collagen, although higher in the control group, was not significantly so at any time during the study (p=0.103 after seven days and p=0.549 after fourteen days). The average of fibroblasts per field was lower after seven days (p=0.0001) and after fourteen days (p=0.0000). CONCLUSION: Under the conditions of this experiment, nicotine reduced the fibroblast population without modifying collagen density significantly.

OBJETIVO: Estudar a densidade de colágeno e a população de fibroblastos em feridas cutâneas de ratos sob a influência da nicotina. MÉTODOS: Analisaram-se as cicatrizes de feridas abdominais de ratos. Foi administrada 2 mg/kg/d de nicotina, por via subcutânea aos animais do grupo experimento e a solução usada como veículo para os animais do grupo controle. O tratamento foi iniciado sete dias antes do ato operatório e mantido por sete ou quatorze dias no pós-operatório. As cicatrizes ressecadas foram preparadas para estudo histo-patológico. Cortes histológicos foram corados pelo Sirius Supra red F3BA para a análise do colágeno e submetidos à exame pela técnica imuno-histoquímica permitiram reconhecer a população de fibroblastos. RESULTADOS: Verificou-se que não existiu diferença significante na densidade de colágeno tipo I, na avaliação feita com sete dias (p=0,912) e com 14 dias (p=0,211). O grupo controle mostrava mais colágeno tipo III com sete dias (p=0,004), mas aos 14 dias não havia diferença significante (p=0,720). A quantificação do colágeno total, embora fosse maior no grupo controle, não o foi de forma significante em nenhum dos tempos estudados (p=0,103 aos sete dias e p=0,549 aos 14 dias). A média de fibroblastos por campo esteve diminuída na avaliação de sete dias (p=0,0001) e na de quatorze dias (p=0,0000). CONCLUSÃO: Nas condições do experimento, a nicotina promoveu diminuição da população de fibroblastos sem modificar a densidade do colágeno de forma significante.

A influência da nicotina na densidade de colágeno em cicatrizes cutâneas, em ratos / The influence of nicotine on the density of collagen in cutaneous scars in rats

OBJETIVO: Estudar a reação inflamatória e a deposição de colágeno na cicatrização de feridas cutâneas sob a influência da nicotina. MÉTODOS: Analisaram-se as cicatrizes de feridas abdominais de ratos tratados com nicotina, 2 mg/kg/d, comparando-as às de ratos controle. O tratamento foi iniciado sete dias antes do ato operatório e mantido por sete ou 14 dias, no pós-operatório. Os cortes histológicos foram corados pela hematoxilina e eosina e neles por meio de escores estabelecidos, reconheceu-se a intensidade e o tipo da reação inflamatória. Cortes histológicos corados pelo Sirius Supra red F3BA permitiram reconhecer a densidade do colágeno. RESULTADOS: Não houve diferença quanto à intensidade da reação inflamatória na análise de sete dias (p=0,165) e nem na de 14 dias (p=0,684). Pôde-se verificar que não existiu diferença significante na densidade de colágeno tipo I, na avaliação feita com sete dias (p=0,912) e com 14 dias (p=0,211). O grupo controle mostrava mais colágeno tipo III com sete dias (p=0,004), mas aos 14 não havia diferença significante (p=0,720). A quantificação do colágeno total, embora fosse maior no grupo controle, não o foi de forma significante em nenhum dos tempos estudados (p=0,103 aos sete e p=0,549 aos 14 dias). CONCLUSÃO: Não houve, nas cicatrizes dos animais tratados com nicotina, em relação aos controles, diferença quanto à intensidade do processo inflamatório, nem quanto à densidade do colágeno.

OBJECTIVE: To study the inflammatory reaction and deposition of collagen in the healing of cutaneous injuries under the influence of nicotine. METHODS: The scars of abdominal injuries in rats were analyzed, which had been treated with nicotine, 2 mg/kg/d, and compared with those of control rats. Treatment was begun seven days prior to operation and was maintained for seven or fourteen days after surgery. The histological cuts were stained with hematoxylin and eosin and through the established scores the intensity and type of inflammatory reaction was identified. Histological cuts stained by Sirius Supra red F3BA enabled the identification of the collagen density. RESULTS: There was no difference in intensity of the inflammatory reaction after seven days (p=0.165), nor after fourteen days (p=0.684). There was no significant difference in the type I collagen density in the evaluation carried out after seven days (p=0.912) and after fourteen days (p=0,211). The control group had more type III collagen after seven days (p=0.004), but after fourteen days there was no significant difference (p=0.720). Although the total quantification of collagen was higher in the control group, there was no significant difference at any time during this study (p=0.103 after seven days and p=0.549 after fourteen days). CONCLUSION: In the scars of the animals treated with nicotine in comparison with the control group, there was no difference in the intensity of the inflammatory process, nor in collagen density.

Effects of hyperglycemia and aging on the healing of colonic anastomoses in rats.

INTRODUCTION: Despite the significant advances in the knowledge of the healing process, there is a limited number of studies demonstrating the relationships of this healing with ageing and elevated levels of glycemia. PURPOSE: To evaluate the effects of ageing and hyperglycemia on the healing of colonic anastomosis. METHODS: 138 young and old male rats were utilized. Some of them were normoglycemic and others had hyperglycemia induced by streptozocin (50mg/kg). They were maintained under control for 90 days. They were then submitted to a termino-terminal anastomosis in the left colon. On the third, seventh and fourteenth days after surgery, their resistance was evaluated and a histopathological study of the anastomosis was carried out. RESULTS: Gain in resistance was similar for both groups. The additive effect of age with hyperglycemia made a significant difference to the collagen I (p<0.001), III (p=0.022) and total (p<0.001). Among the old animals, the glycemia was a determining factor for the occurrence of a significant difference in total collagen (p=0.029) and collagen I (p=0.013). Among the normoglycemics, age determined a lower density of collagen I (p=0.002). CONCLUSION: There is delayed collagen synthesis and maturation of the scars of older animals, a situation that becomes more serious in older hyperglycemic animals, but insufficient to adversely affect the gain in resistance.

Effects of hyperglycemia and ageing on the healing of colonic anastomoses in rats / Efeitos da hiperglicemia e do envelhecimento na cicatrização de anastomoses colônicas, em ratos

INTRODUCTION: Despite the significant advances in the knowledge of the healing process, there is a limited number of studies demonstrating the relationships of this healing with ageing and elevated levels of glycemia. PURPOSE: To evaluate the effects of ageing and hyperglycemia on the healing of colonic anastomosis. METHODS: 138 young and old male rats were utilized. Some of them were normoglycemic and others had hyperglycemia induced by streptozocin (50mg/kg). They were maintained under control for 90 days. They were then submitted to a termino-terminal anastomosis in the left colon. On the third, seventh and fourteenth days after surgery, their resistance was evaluated and a histopathological study of the anastomosis was carried out. RESULTS: Gain in resistance was similar for both groups. The additive effect of age with hyperglycemia made a significant difference to the collagen I (p<0.001), III (p=0.022) and total (p<0.001). Among the old animals, the glycemia was a determining factor for the occurrence of a significant difference in total collagen (p=0.029) and collagen I (p=0.013). Among the normoglycemics, age determined a lower density of collagen I (p=0.002). CONCLUSION: There is delayed collagen synthesis and maturation of the scars of older animals, a situation that becomes more serious in older hyperglycemic animals, but insufficient to adversely affect the gain in resistance.

INTRODUÇÃO: Apesar dos significantes avanços no conhecimento do processo cicatricial há um restrito número de estudos demonstrando as relações deste reparo com o envelhecimento e com níveis elevados de glicemia. OBJETIVO: Avaliar os efeitos do envelhecimento e da hiperglicemia na cicatrização de anastomoses colônicas. MÉTODOS: Utilizaram-se 138 ratos machos, adultos jovens e velhos. Parte deles era normoglicêmico e parte teve hiperglicemia induzida pelo streptozocin (50mg/kg). Foram mantidos controlados por 90 dias. Após fez-se uma anastomose término-terminal no cólon esquerdo. No 3.º, 7.º e 14.º dia de pós-operatório avaliou-se a resistência e fez-se o estudo histo-patológico da anastomose. RESULTADOS: O ganho de resistência foi semelhante entre os grupos. O efeito aditivo da idade com a hiperglicemia determinou diferença significativa nos colágenos I (p<0,001), III (p=0,022) e total (p<0,001). Entre os velhos a glicemia foi determinante para ocorrer diferença significativa no colágeno total (p=0,029) e colágeno I (p=0,013). Entre os normoglicêmicos a idade determinou menor densidade de colágeno I (p=0,002). CONCLUSÃO: Existe atraso na síntese do colágeno e na maturação das cicatrizes nos animais velhos, situação que se agrava nos animais velhos e hiperglicêmicos, não suficiente para prejudicar o ganho de resistência.

[The influence of nicotine on the density of collagen in cutaneous scars in rats]. / A influência da nicotina na densidade de colágeno em cicatrizes cutâneas, em ratos.

OBJECTIVE: To study the inflammatory reaction and deposition of collagen in the healing of cutaneous injuries under the influence of nicotine. METHODS: The scars of abdominal injuries in rats were analyzed, which had been treated with nicotine, 2 mg/kg/d, and compared with those of control rats. Treatment was begun seven days prior to operation and was maintained for seven or fourteen days after surgery. The histological cuts were stained with hematoxylin and eosin and through the established scores the intensity and type of inflammatory reaction was identified. Histological cuts stained by Sirius Supra red F3BA enabled the identification of the collagen density. RESULTS: There was no difference in intensity of the inflammatory reaction after seven days (p=0.165), nor after fourteen days (p=0.684). There was no significant difference in the type I collagen density in the evaluation carried out after seven days (p=0.912) and after fourteen days (p=0,211). The control group had more type III collagen after seven days (p=0.004), but after fourteen days there was no significant difference (p=0.720). Although the total quantification of collagen was higher in the control group, there was no significant difference at any time during this study (p=0.103 after seven days and p=0.549 after fourteen days). CONCLUSION: In the scars of the animals treated with nicotine in comparison with the control group, there was no difference in the intensity of the inflammatory process, nor in collagen density.

The influence of hypothyroidism on liver regeneration: an experimental study in rats.

BACKGROUND: The influence of hypothyroidism in liver regeneration has been a controversial opinions. PURPOSE: The aim of this study is to identify the relationship between hypothyroidism and liver regeneration in rats. METHODS: Forty male Wistar rats divided into two groups of 20 specimens each. One group (C) consisted of euthyroid rats, and the other (H) of hypothyroid rats. All the animals were anesthetized with xylazine and ketamine and subjected to a longitudinal incision in the anterior cervical region. The thyroid was completely resected in group H and left intact in group C. Ten days after the first surgery, both groups of rats were weighed and submitted to partial hepatectomy, in which the left lateral and median lobes were resected and weighed. Examinations were carried out after 24 hours and, on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in five fields; and the percentage of PCNA-positive nuclei in five fields. RESULTS: Using KWON's formula, the regeneration rate for Group C after 24 hours was 58.49% whereas that for Group H was 50.42% (p=0.0165). After 7 days, the regeneration rate for Group C was 93.04% and Group H 93.74% (p=0.2165). The average number of mitotic figures after 24 hours was 14 +/- 1.5 for Group C and 9.8 +/- 2.2 for Group H (p=0,00016). After 7 days the corresponding figures were 5.4 +/-1.1 and 5.1+/- 1.2 (p=0,6343). The average number of PCNA-positive nuclei after 24 hours was 13.55+/- 3.84 in Group C and 7.7 +/- 2.11 in Group H (p =0,0006)). The corresponding figures after 7 days were 3.5 +/- 2.39 for Group C and 4.11 +/-1.90 for Group H (p>0.05). CONCLUSION: We conclude that hypothyroidism in rats causes a delay in hepatic regeneration in the first 24 hours, but that after seven days the rate of regeneration is equal to that in euthyroid rats.

The influence of hypothyroidism on liver regeneration: an experimental study in rats

BACKGROUND: The influence of hypothyroidism in liver regeneration has been a controversial opinions. PURPOSE: The aim of this study is to identify the relationship between hypothyroidism and liver regeneration in rats. METHODS: Forty male Wistar rats divided into two groups of 20 specimens each. One group (C) consisted of euthyroid rats, and the other (H) of hypothyroid rats. All the animals were anesthetized with xylazine and ketamine and subjected to a longitudinal incision in the anterior cervical region. The thyroid was completely resected in group H and left intact in group C. Ten days after the first surgery, both groups of rats were weighed and submitted to partial hepatectomy, in which the left lateral and median lobes were resected and weighed. Examinations were carried out after 24 hours and, on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in five fields; and the percentage of PCNA-positive nuclei in five fields. RESULTS: Using KWON's formula, the regeneration rate for Group C after 24 hours was 58.49 percent whereas that for Group H was 50.42 percent (p=0.0165). After 7 days, the regeneration rate for Group C was 93.04 percent and Group H 93.74 percent (p=0.2165). The average number of mitotic figures after 24 hours was 14 ± 1.5 for Group C and 9.8 ± 2.2 for Group H (p=0,00016). After 7 days the corresponding figures were 5.4 ± 1.1 and 5.1 ± 1.2 (p=0,6343). The average number of PCNA-positive nuclei after 24 hours was 13.55 ± 3.84 in Group C and 7.7 ± 2.11 in Group H (p =0,0006)). The corresponding figures after 7 days were 3.5 ± 2.39 for Group C and 4.11 ± 1.90 for Group H (p>0.05). CONCLUSION: We conclude that hypothyroidism in rats causes a delay in hepatic regeneration in the first 24 hours, but that after seven days the rate of regeneration is equal to that in euthyroid rats.

BACKGROUND: A influência do hipotireoidismo na regeneração hepatica tem opiniões controvérsas. OBJETIVO: Identificar a relação entre o hipotireoidismo e a regeneração hepatica, em ratos. MÉTODOS: Quarenta ratos Wistar, machos, divididos em dois grupos de 20 animais. Um grupo (C) constituído de ratos eutireoideanos e outro (H) de ratos hipotireoideanos. Todos os animais foram anestesiados com xilasina e quetamina e submetidos a uma incisão cervical longitudinal. A tireóide foi completamente ressecada no animais do grupo H e deixada intacta no grupo C. Dez dias após a primeira intervenção ambos os grupos de ratos foram pesados e submetidos à hepatectomia parcial, retirando-se os lobos lateral esquerdo e mediano, que foram pesados. Foram examinados com 24 horas e com 7 dias usando-se 3 métodos: formula de KWON et al. que identifica o aumento de volume; contagem de figures de mitose em cinco campos e de núcleos PCNA positivos em cinco campos. RESULTOS: Usando a formula de KWON et al. a taxa de regeneração do grupo C, após 24 horas, foi de 58.49 por cento enquanto que a do grupo H foi de 50.42 por cento (p=0.0165). Após 7 dias, a taxa de regeneração no grupo C foi de 93.04 por cento e do grupo H 93.74 por cento (p=0.2165). A média de figures de mitose após 24 horas foi de 14 ± 1.5 no grupo C e de 9.8 ± 2.2 no groupo H (p=0,00016). Após 7 dias foi de 5.4 ± 1.1 e 5.1 ± 1.2 (p=0,6343). A média de núcleos PCA positivos, após 24 horas, foi de 13.55 ± 3.84 no grupo C e 7.7 ± 2.11 no grupo H (p =0,0006)). Com 7 dias foi de 3.5 ± 2.39 no groupo C e de 4.11 ± 1.90 for Group H (p>0.05). CONCLUSÃO: Concluiu-se que o hipotireoidismo, em ratos, causa atraso da regeneração hepatica nas primeiras 24 horas, mas após 7 dias a regeneração se equivale à dos ratos eutireoideanos.

[The healing influenced by hypothyroidism and elderly. Study of intestinal anastomosis healing in rats]. / O processo de cicatrização influenciado pelo hipotireoidismo e pelo envelhecimento. Estudo da cicatrização de anastomoses intestinais, em ratos.

PURPOSE: The aging of the population has led to an increased number of interventions in elderly patients, with hypothyroidism, even at the subclinical level, being a common situation among these patients. The objective of the present study was to determine the influence of hypothyroidism on the healing process of colon anastomoses in aged rats. METHODS: 96 male Wistar rats were used, 48 of them young and 48 old. Half the young animals and half the old ones were euthyroid and half were hypothyroid. Hypothyroidism was obtained by total thyroidectomy. Thirty days after surgery the animals were submitted to median laparotomy followed by transverse colotomy of the left colon with end-to-end anastomosis and laparorrhaphy. Six animals from each group were submitted to euthanasia by drawing lots on the 3rd, 7th and 14th postoperative day and submitted to macroscopic, resistance, and histopathological analysis of the anastomoses. RESULTS: No dehiscence was observed and the gain of resistance and the general histological evolution in terms of epithelialization and inflammatory reaction was similar in all groups. Analysis of total collagen content revealed that the anastomoses of young and old animals showed the same behavior on the 3rd day, although less collagen was observed in hypothyroid animals (YN x YH p = 0.0000; ON x OH p = 0.0000). This behavior persisted on the 7th and 14 day. Less collagen I was present in the anastomoses of hypothyroid animals on the 3 (YN x YH p = 0.0015; ON x OH p = 0.0000), 7th (YN x YH p = 0.0006; ON x OH p = 0.0001) and 14th day (YN x YH p = 0.0181; ON x OH p = 0.0057), the same occurring for collagen III on the 3rd (x YH p = 0.0007; ON x OH p = 0.0260), 7th (YN x YH p = 0.0160; ON x OH p = 0.2670) and 14th day (YN x YH p = 0.0000; ON x OH p = 0.0030). CONCLUSION: Analysis of the results permitted us to conclude that lower collagen concentration du to low synthesis and delayed scar maturation in the anastomoses occurred and was much more due to hypothyroidism than to aging.

O processo de cicatrização influenciado pelo hipotireoidismo e pelo envelhecimento: estudo da cicatrização de anastomoses intestinais, em ratos

TURPOSE: The aging of the population has led to an increased number of interventions in elderly patients, with hypothyroidism, even at the subclinical level, being a common situation among these patients. The objective of the present study was to determine the influence of hypothyroidism on the healing process of colon anastomoses in aged rats. METHODS: 96 male Wistar rats were used, 48 of them young and 48 old. Half the young animals and half the old ones were euthyroid and half were hypothyroid. Hypothyroidism was obtained by total thyroidectomy. Thirty days after surgery the animals were submitted to median laparotomy followed by transverse colotomy of the left colon with end-to-end anastomosis and laparorrhaphy. Six animals from each group were submitted to euthanasia by drawing lots on the 3rd, 7th and 14th postoperative day and submitted to macroscopic, resistance, and histopathological analysis of the anastomoses. RESULTS: No dehiscence was observed and the gain of resistance and the general histological evolution in terms of epithelialization and inflammatory reaction was similar in all groups. Analysis of total collagen content revealed that the anastomoses of young and old animals showed the same behavior on the 3rd day, although less collagen was observed in hypothyroid animals (YN x YH p=0.0000; ON x OH p=0.0000). This behavior persisted on the 7th and 14th day. Less collagen I was present in the anastomoses of hypothyroid animals on the 3rd (YN x YH p=0.0015; ON x OH p=0.0000), 7th (YN x YH p=0.0006; ON x OH p=0.0001) and 14th day (YN x YH p=0.0181; ON x OH p=0.0057), the same occurring for collagen III on the 3rd (x YH p=0.0007; ON x OH p=0.0260), 7th (YN x YH p=0.0160; ON x OH p=0.2670) and 14th day (YN x YH p=0.0000; ON x OH p=0.0030). CONCLUSION: Analysis of the results permitted us to conclude that lower collagen concentration due to low synthesis and delayed scar maturation in the anastomoses occurred and was much more due to hypothyroidism than to aging.

OBJETIVO: O envelhecimento da população tem feito crescer o número de intervenções em pacientes idosos, sendo o hipotireoidismo, ainda que sub-clínico, é uma situação bastante comum nestes doentes. O presente estudo busca conhecer a influência do hipotireoidismo no processo de cicatrização de anastomoses colônicas em ratos idosos. MÉTODO: Utilizaram-se 96 ratos Wistar, machos; 48 deles jovens e 48 velhos. Metade dos animais jovens e metade dos velhos eram eutireoideanos e metade eram hipotireoideanos. Conseguiu-se o hipotireoidismo por meio de tireoidectomia total. Após 30 dias, fez-se uma laparotomia mediana seguida de colotomia transversa de cólon esquerdo com anastomose término-terminal e laparorrafia. No 3.º, 7.º e 14.º dias de pós-operatório, sorteados, 6 animais de cada grupo, que foram submetidos à eutanásia. Fez-se a análise macroscópica das anastomoses, da resistência e estudo histopatológico. RESULTADOS: Não se detectaram deiscências e o ganho de resistência e a evolução histológica geral, considerando epitelização e reação inflamatória foi semelhante em todos os grupos. A análise do conteúdo total de colágeno revelou, no 3.º dia, que as anastomoses de jovens e velhos tinham o mesmo comportamento, porém via-se menos colágeno nas anastomoses dos animais com hipotireoidismo (JN x JH p=0,0000; VN x VH p=0,0000). Este comportamento se manteve no 7.º e no 14.º dia. A presença de colágeno I era menor nas anastomoses dos animais hipotireoideanos no 3.º dia (JN x JH p=0,0015; VN x VH p=0,0000), no 7.º dia (JN x JH p=0,0006; VN x VH p=0,0001) e no 14.º dia (JN x JH p=0,0181; VN x VH p=0,0057) o mesmo acontecendo com o colágeno III, no 3.º dia (x JH p=0,0007; VN x VH p=0,0260), no 7.º dia (JN x JH p=0,0160; VN x VH p=0,2670) e no 14.º dia (JN x JH p=0,0000; VN x VH p=0,0030). CONCLUSÃO: A análise dos resultados permite concluir que existe diminuição da concentração de colágeno decorrente da baixa da síntese e retardo de maturação das cicatrizes das anastomoses muito mais às custas do hipotireoidismo do que do envelhecimento.