Protective effect of the standardized leaf extract of Ginkgo biloba (EGb761) against hypertension-induced renal injury in rats.

BACKGROUND: Ginkgo biloba leaves extract has been widely used worldwide to protect against oxidative stress-induced cell damage and improves blood circulation. METHODS: The potential protective role of the standardized leaf extract of Ginkgo biloba (EGb761) on hypertension-induced renal injury was investigated in rats. Hypertension was induced in rats by L-NAME. RESULT: Repeated treatment with EGb761 produced progressive reductions in the systolic, diastolic and mean arterial blood pressure. Also, EGb761 increased the progressive reductions in blood pressure induced by losartan. Hypertension-induced marked elevation of renal malondialdehyde (MDA) and nitrite levels and reduction of reduced glutathione (GSH) level were inhibited by EGb761. In addition, hypertension-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß)) levels in renal tissues were inhibited by EGb761. Also, treatment with EGb761 inhibited hypertension-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1B in the kidney tissues. EGb761 enhanced losartan effects on renal tissues oxidative stress, nitrite, and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1B. effects. CONCLUSIONS: These results indicate that EGb761 has the ability to protect against hypertension-induced renal injury.

Protective effect of the standardized extract of ginkgo biloba (EGb761) against hypertension with hypercholesterolemia-induced renal injury in rats: Insights in the underlying mechanisms.

The potential protective role of the standardized leaf extract of ginkgo biloba (EGb761) on hypertension with hypercholesterolemia-induced renal injury was investigated in rats. Hypertension was induced by L-N(G)-nitroarginine methyl ester (L-NAME) and hypercholesterolemia was induced by feeding rats with a diet containing 1% cholesterol. In these animals repeated treatment with EGb761 produced a progressive reduction in the systolic, diastolic and mean arterial blood pressure (BP). EGb761 increased the progressive reduction in the systolic, diastolic and mean arterial BP induced by repeated administration of losartan with simvastatin. EGb761 corrected the compromised serum lipid profile and enhanced the effect of losartan with simvastatin on lipid profile. EGb761 protected against hypertension with hypercholesterolemia-induced renal injury as assessed by measurement of serum renal function markers and by histopathological examination. EGb761 enhanced the renoprotective effect of losartan with simvastatin in these rats. Concomitantly, hypertension with hypercholesterolemia-induced elevation of renal tissue malondialdehyde (MDA) and nitrite levels and reduction of intracellular reduced glutathione (GSH) level were inhibited by repeated treatment with EGb761. In addition, hypertension with hypercholesterolemia-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) levels in renal tissues were inhibited by treatment with EGb761. Also, EGb761 inhibited hypertension with hypercholesterolemia-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1ß in the kidney tissues. Losartan with simvastatin produced similar effects on renal tissues oxidative stress, nitrite and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1ß. EGb761 enhanced losartan with simvastatin effects. These results indicate that EGb761 has the ability to protect against hypertension with hypercholesterolemia-induced renal injury. The ability of EGb761 to provide this renoprotective effect may positively correlate, besides its antihypertensive and antihypercholesterolemic effects, to its ability to suppress renal oxidative stress, nitrosative stress and inflammation.

Suppression of transforming growth factor-beta1 expression in keloids after cryosurgery.

The biological mechanism underlying cryosurgical treatment of keloids remains unclear. Transforming growth factor-beta1 (TGF-ß1) has been implicated in the pathogenesis of keloids and was reported to be the target of several therapeutic modalities. However, the effect of cryosurgery on its expression in keloid tissue has not been yet investigated. In this study, 26 consecutive keloid patients were treated with cryosurgery for 2-6 sessions. Keloids were biopsied before starting cryosurgery and after two treatment sessions for the immunohistochemical evaluation of TGF-ß1 expression. The average volume reduction, after two treatment sessions (in 22 patients completing the study) was 68.77 ± 15.82%. Dermal overexpression of TGF-ß1 was demonstrated in all keloid specimens before treatment. Following therapy, significant reduction of that expression was detected in all keloid specimens (P = 0.016). In addition to attesting the clinical efficacy of cryosurgery, our findings indicate that cryosurgery effectively suppressed TGF-ß1 expression, possibly contributing to keloid regression.

Expression of survivin in squamous cell carcinoma and transitional cell carcinoma of the urinary bladder: a comparative immunohistochemical study.

PURPOSE: To compare the expression of survivin and its association with clinicopathological criteria in major types of urinary bladder carcinoma, specifically, transitional cell carcinoma with and without squamous differentiation and squamous cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for survivin and Ki67 was performed on paraffin-embedded sections of 104 carcinomas: 52 transitional cell carcinoma, 20 transitional cell carcinoma with squamous differentiation, and 32 squamous cell carcinoma. Expression of survivin in >10% of tumor cells was described as altered survivin status. Ki67 staining in >20% of tumor cells was described as a high proliferation index. RESULTS: Altered survivin expression was detected in 60/104 specimens (58%) and was significantly more frequent in transitional cell carcinoma (78%) than in squamous cell carcinoma (38%) or transitional cell carcinoma with squamous differentiation (40%) (p<0.0001). In transitional cell carcinoma but not in squamous cell carcinoma, altered survivin status was associated with higher tumor grade, higher proliferation index, and recurrence. In the whole specimens, altered survivin expression was significantly associated with advanced stage (p<0.001), recurrence (p=0.005), distant metastasis (p<0.001), and death (p=0.001). In the multivariate analysis, altered survivin was an independent poor prognostic factor for recurrence. CONCLUSIONS: Unlike in transitional cell carcinoma, alteration of survivin expression in squamous cell carcinoma occurs less frequently and is not associated with features of tumor aggression or patient outcome. These findings raise a question: are urinary bladder carcinoma patients with squamous cell carcinoma type suitable candidates for survivin vaccine? This is an important question to be answered before approving the vaccine in management.

Intralesional vs. contact cryosurgery in treatment of keloids: a clinical and immunohistochemical study.

BACKGROUND: Cryosurgery is a safe and effective treatment of keloids. Intralesional cryosurgery has been shown to bring about significant improvement in keloids. The histopathological and immunohistochemical changes in keloids following cryosurgery are not well-assessed. METHODS: Twenty-three patients with 66 keloids were treated with either the contact (cryoprobe) method or intralesional cryosurgery. Keloid specimens were obtained before treatment and after two sessions of treatment for evaluation of keloid pathology and immunohistochemical changes in expression of vascular endothelial growth factor (VEGF) and tenascin C induced by both cryosurgical techniques. RESULTS: A better therapeutic response was detected after intralesional cryosurgery (excellent response [ER], 87%) than contact cryosurgery (ER, 60%; P < 0.05). The intralesional technique achieved higher rates of flattening after the first two sessions (ER in 61.3% and 22.9%, respectively; P < 0.05) and caused fewer side effects compared with the contact method. Both cryosurgical methods resulted in a significant decrease in VEGF and tenascin C expression in keloids. CONCLUSIONS: Intralesional cryosurgery is superior to contact cryosurgery in terms of efficacy and safety. Both techniques may have beneficial effects on keloids, at least partially, through the modulation of VEGF and tenascin C expression.

Cardiac histopathological and immunohistochemical changes due to electric injury in rats.

It has been a puzzling forensic task to determine the cause of death as a result of electric shock in the absence of recognizable skin marks or definite postmortem morphological findings. In forensic pathology, while classical macroscopic and microscopic morphology remain core procedures to investigate deaths, a variety of subsidiary measures has been developed and incorporated to detail that pathology. C-fos, one of a small group of genes called primary response genes and its protein product, fos, are crucial elements of complex signaling mechanisms believed to be responsible for cell response to stimulation. It has been found that c-fos plays a significant role in myocardial lesions, and has close relation to injury repair of the molecule. The aim of this study was to detect the histopathological findings in the myocardium after fatal and non-fatal electrical injury in rats and to investigate the potential role of c-fos expression using immunohistochemistry to distinguish antemortem from postmortem electrocution. Forty adult female rats were implemented and randomly divided into four groups (A, B, C and D). Group (A) rats were subjected to instantaneous antemortem electricity and their hearts were collected either immediately (A1) or after an hour (A2) before being subjected to cervical dislocation. Group (B) rats were electrically injured instantaneously postmortem, hearts were collected immediately (B1) or an hour later (B2) while Group (C) rats were electrified up to death, and their hearts were also gathered either immediately (C1) or after an hour (C2) from electrocution. Lastly, another group of rats served as a control group (Group D). Subgroup (D1): rats were clamped but not electrified, before death and another group of rats were clamped but not electrified, after being killed by cervical dislocation. Sections from the hearts of all groups were fixed in formalin and routinely processed. The c-fos oncogene expression was evaluated in all groups by immunohistochemistry. Significant histopathological findings were detected in groups A and C. Few c-fos oncogene protein positive cardiomyocyte nuclei were seen in rats of groups (A1) and (B1). Additionally, increased expression in rats of groups C1, C2 and A2 were observed. On the other hand, no c-fos protein expression was seen either in the control (groups D1 and D2) or in group B2. Significant differences (p < 0.001) in c-fos expression were observed among rats of groups with antemortem electric injury (A1, A2) and those of postmortem injury (B1 and B2). Thus, in addition to classical histopathological methods, c-fos can be regarded as a target in identifying electrical injury, and can be used as an indicator to distinguish antemortem from postmortem electric shock.