Anatomical site differences of sodium lauryl sulfate-induced irritation: randomized controlled trial.

BACKGROUND: Sodium lauryl sulfate (SLS)-induced contact dermatitis is a commonly used model for testing the effects of different topical formulations. According to the guidelines, the volar forearms are the preferred testing site; however, other anatomical locations have been used in previous research, particularly the upper back as the clinically used site for testing different antigens. OBJECTIVES: To investigate the existence of anatomical variations of the skin response to irritation and its effects on the response to treatment. METHODS: Irritation was induced with SLS on symmetrical sites on both forearms and sides of the upper back with additional sites exposed to water as controls. Half of the sites were treated with emollient cream while the other half were left untreated. Irritation was assessed using bioengineering methods and clinical scoring. The trial was registered at ClinicalTrials.gov as NCT03231813. RESULTS: Upper back skin showed higher reactivity to irritants with stronger barrier disruption (measured by Tewameter® , 80·2 ± 18·3 vs. 48·0 ± 24·2 g m-2  h-1 ), more pronounced erythema (measured by Mexameter® , 186·5 ± 88·4 vs. 92·1 ± 58·2 arbitrary units) and dryness (measured by Corneometer® , -28·6 ± 14·5 vs. 2·7 ± 16·9 arbitrary units). Skin recovery rates were also influenced by anatomical location with the upper back showing faster recovery (316·7 ± 223·1 vs. 156·2 ± 198·5). Treatment did not lead to improvement in measured parameters, regardless of anatomical location. CONCLUSIONS: The skin's reaction to irritant and recovery was dependent on anatomical location. The location where testing was conducted should always be reported, as treatments tested across different locations could not be directly compared with each other.

Cardiovascular effects in vitro of aqueous extract of wild strawberry (Fragaria vesca, L.) leaves.

In contrast to the strawberry fruits, strawberry leaves as a source of bioactive compounds with potentially beneficial biological effects have been largely overlooked. In this study we examined direct, dose-dependent effects of wild strawberry (Fragaria vesca, L.) leaves aqueous extract, in two experimental models and animal species, the isolated guinea pig hearts and rat aortic rings. Vasodilatory potential of the wild strawberry leaves extract was compared with vasodilatory activity of aqueous extract of hawthorn (Crataegus oxycantha, L) leaves with flowers, which can be regarded as a reference plant extract with a marked vasodilatory activity. The extracts were analysed by their "phenolic fingerprints", total phenolic content and antioxidative capacity. Their vasodilatory activity was determined and compared in the isolated aortic rings from 24 rats that were exposed to the extracts doses of 0.06, 0.6, 6, and 60 mg/100ml. Both extracts induced similar, dose-dependent vasodilation. Maximal relaxation was 72.2+/-4.4% and 81.3+/-4.5%, induced by the strawberry and hawthorn extract, respectively. To determine vasodilatory mechanisms of the wild strawberry leaves extract, endothelium-denuded and intact rings exposed to nitric oxide (NO) synthase inhibitor L-NAME or cyclooxygenase inhibitor indomethacin were used. Removal of the endothelium prevented and exposure to L-NAME or indomethacin strongly diminished the vasodilatatory response to the extract. In the isolated hearts (n=12), the wild strawberry extract was applied at concentrations of 0.06, 0.18, 0.6, and 1.8 mg/100ml. Each dose was perfused for 3.5 min with 15 min of washout periods. Heart contractility, electrophysiological activity, coronary flow and oxygen consumption were continuously monitored. The extract did not significantly affect heart rate and contractility, main parameters of the cardiac action that determine oxygen demands, while coronary flow increased up to 45% over control value with a simultaneous decrease of oxygen extraction by 34%. The results indicate that the aqueous extract of wild strawberry leaves is a direct, endothelium-dependent vasodilator, action of which is mediated by NO and cyclooxygenase products and which potency is similar to that of the hawthorn aqueous extract.

Dose dependent effects of standardized nose-horned viper (Vipera ammodytes ammodytes) venom on parameters of cardiac function in isolated rat heart.

Direct, dose dependent effects of the nose-horned vipers (Vipera ammodytes ammodytes) venom on various parameters of cardiac action in isolated rat hearts were examined. Biochemical (protein content, SDS polyacrylamide gel electrophoresis) and biological (minimum haemorrhagic and necrotizing dose and lethal dose (LD(50))) characterization of the venom was performed before testing. The hearts were infused with venom doses of 30, 90 and 150 microg/mL for 10 min followed by 30 min of wash out period. Left ventricular pressure, coronary flow, heart rate, atrioventricular conduction, myocardial oxygen consumption, incidence and duration of arrhythmias were measured and relative cardiac efficiency was calculated. Cardiac CPK, LDH, AST and troponin I were measured as biochemical markers of myocardial damage. The venom caused dose dependent electrophysiological instability and depression of contractility and coronary flow. Effects on the heart rate were biphasic; transient increase followed by significant slowing of the frequency. Relative cardiac efficiency decreased as oxygen consumption remained high relative to the heart rate-contractility product, indicating purposeless expenditure of oxygen and energy. Effects by the dose of 30 microg/mL were highly reversible while the dose of 90 mug/mL caused damages that were mostly irreversible. The dose of 150 mug/mL induced irreversible asystolic cardiac arrest.

131 I-induced changes in rat thyroid gland function.

Therapeutic doses of (131)I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of (131)I (64-277 microCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before (131)I administration (4-month-old animals) and three times following (131)I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 +/- 8.16 to 55.0 +/- 6.1 nM in the control group and from 69.4 +/- 6.9 to 25.4 +/- 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after (131)I administration to rats, which was not (131)I dose dependent.

131I-induced changes in rat thyroid gland function

Therapeutic doses of 131I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of 131I (64-277 µCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before 131I administration (4-month-old animals) and three times following 131I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 ± 8.16 to 55.0 ± 6.1 nM in the control group and from 69.4 ± 6.9 to 25.4 ± 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after 131I administration to rats, which was not 131I dose dependent.

Effects of hyperbaric oxygen therapy on experimental burn wound healing in rats: a randomized controlled study.

A body of data supports the efficacy of hyperbaric oxygen (HBO2) therapy in the treatment of thermal burns, but the role of HBO2 in the treatment of burn injury remains a subject of controversy. The aim of this study was to evaluate possible positive effects of HBO2 on the experimental burn wound healing. Deep second degree burns were produced on the depilated backs of 70 male Wistar rats using a validated burn protocol. The animals were assigned randomly to one of two groups: 35 to the control group, which was treated with silver sulphadiazine and placebo gas, and 35 to the experimental group, which was treated with silver sulphadiazine and HBO2. The main outcome measure was wound healing, characterized by formation of post-burn edema, neoangiogenesis, number of regeneratory active follicles, necrosis staging, margination of leukocytes, and time of epithelization. A significant reduction of the post-burn edema after treatment with HBO2 (p = 0.009) was found. HBO2 had a beneficial effect on neoangiogenesis (p = 0.009). The number of preserved regeneratory active follicles was significantly higher (p = 0.009) and epithelial regeneration was more rapid in the experimental group (p = 0.048). There were no significant differences for margination of leukocytes (p = 0.55) or necrosis staging (p = 1.00). These data further support earlier conclusions that HBO2 is beneficial in the healing of burn wounds.

Gender differences in antioxidant capacity of rat tissues determined by 2,2'-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays.

Differences in susceptibility to oxidative stress between males and females have been postulated. Several methods have been developed to assess the total antioxidant capacity of human serum or plasma, but just recently some of them were employed for measurement of antioxidant capacity of tissues. In this study, we measured and compared antioxidant capacity of heart, kidney, liver and brain tissues of male and female rats. Antioxidant capacity was determined using 2,2'-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays. In the same samples, lipid peroxidation products of these tissues were analysed using thiobarbituric acid reactive substances (TBARS) assays. Antioxidant capacity of heart, kidney and liver tissues was higher in female than male rats for both FRAP and ABTS assays. We found positive correlation between FRAP and ABTS values for all tested tissues. FRAP and ABTS proved to be comparable, simple and quick methods for antioxidant capacity scanning in tissues. TBARS levels differed only for brain tissue, being higher in males. These results indicate stronger defense against oxidative damage in females for all observed tissues. These finding may account for the longer lifespan of females.

Effect of hyperbaric oxygenation on the regeneration of the liver after partial hepatectomy in rats

The aim of the present study was to assess the influence of hyperbaric oxygenation (HBO) on rat liver regeneration before and after partial hepatectomy. Rats were sacrificed 54 h after 15 percent hepatectomy, liver and body weights were measured, and serum alanine transaminase (ALT) and aspartate transaminase (AST) activity and albumin levels were determined. The lipid peroxide level, as indicated by malondialdehyde production in the remnant liver was measured, and liver sections were analyzed by light microscopy. Five groups of 10 rats in each group were studied. The preHBO and pre-hyperbaric pressure (preHB) groups were treated before partial hepatectomy with 100 percent O2 and 21 percent O2, respectively, at 202,650 pascals, daily for 3 days (45 min/day). The control group was not treated before partial hepatectomy and recovered under normal ambient conditions after the procedure. Groups postHBO and postHB were treated after partial hepatectomy with HBO and HB, respectively, three times (45 min/day). The preHBO group presented a significant increase in the initiation of the regeneration process of the liver 54 h postoperatively. The liver/body weight ratio was 0.0618 ± 0.0084 in the preHBO compared to 0.0517 ± 0016 g/g in the control animals (P = 0.016). In addition, the preHBO group showed significant better liver function (evaluated by the lowest serum ALT and AST activities, P = 0.002 and P = 0.008, respectively) and showed a significant decrease in serum albumin levels compared to control (P < 0.001). Liver lipid peroxide concentration was lowest in the preHBO group (P < 0.001 vs control and postHBO group) and light microscopy revealed that the composition of liver lobules in the preHBO group was the closest to normal histological features. These results suggest that HBO pretreatment was beneficial for rat liver regeneration after partial hepatectomy.

Effect of hyperbaric oxygenation on the regeneration of the liver after partial hepatectomy in rats.

The aim of the present study was to assess the influence of hyperbaric oxygenation (HBO) on rat liver regeneration before and after partial hepatectomy. Rats were sacrificed 54 h after 15% hepatectomy, liver and body weights were measured, and serum alanine transaminase (ALT) and aspartate transaminase (AST) activity and albumin levels were determined. The lipid peroxide level, as indicated by malondialdehyde production in the remnant liver was measured, and liver sections were analyzed by light microscopy. Five groups of 10 rats in each group were studied. The preHBO and pre-hyperbaric pressure (preHB) groups were treated before partial hepatectomy with 100% O2 and 21% O2, respectively, at 202,650 pascals, daily for 3 days (45 min/day). The control group was not treated before partial hepatectomy and recovered under normal ambient conditions after the procedure. Groups postHBO and postHB were treated after partial hepatectomy with HBO and HB, respectively, three times (45 min/day). The preHBO group presented a significant increase in the initiation of the regeneration process of the liver 54 h postoperatively. The liver/body weight ratio was 0.0618 +/- 0.0084 in the preHBO compared to 0.0517 +/- 0016 g/g in the control animals (P = 0.016). In addition, the preHBO group showed significant better liver function (evaluated by the lowest serum ALT and AST activities, P = 0.002 and P = 0.008, respectively) and showed a significant decrease in serum albumin levels compared to control (P < 0.001). Liver lipid peroxide concentration was lowest in the preHBO group (P < 0.001 vs control and postHBO group) and light microscopy revealed that the composition of liver lobules in the preHBO group was the closest to normal histological features. These results suggest that HBO pretreatment was beneficial for rat liver regeneration after partial hepatectomy.