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.

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.

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.

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.

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.

[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.

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.

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.