Gypenoside attenuates renal ischemia/reperfusion injury in mice by inhibition of ERK signaling.

Gynostemma pentaphyllum is a traditional Chinese medicine reported to possess a wide range of health benefits. As the major component of G. pentaphyllum, gypenoside (GP) displays various anti-inflammatory and anti-oxidant properties. However, it is unclear whether GP can protect against ischemia/reperfusion (I/R)-induced renal injury, and the underlying molecular mechanisms associated with this process remain unknown. In the present study, a renal I/R injury model in C57BL/6 mice was established. It was observed that, following I/R, serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were significantly increased (P<0.01), indicating renal injury. Pretreatment with GP (50 mg/kg) significantly inhibited I/R-induced upregulation of serum Cr and BUN (P<0.01). Furthermore, renal malondialdehyde levels were significantly reduced in the I/R+GP group, compared with the I/R group (P<0.01), whereas renal tissue superoxide dismutase activity was significantly higher in the I/R+GP group compared with the I/R group (P<0.01). Further investigation demonstrated that pretreatment with GP produced inhibitory effects on the I/R-induced production of pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and interferon-γ (P<0.01). In addition, heme oxygenase 1 (HO-1) expression levels were significantly increased in the I/R group compared with the control (P<0.01), indicating the presence of oxidative damage. However, the I/R-induced upregulation of HO-1 was significantly attenuated by pretreatment with GP (P<0.01), which also suppressed I/R-induced apoptosis by inhibiting pro-apoptotic Bax and upregulating anti-apoptotic Bcl-2 in renal cells (P<0.01). Finally, the activity of ERK signaling was significantly increased in the I/R+GP group compared with the I/R group (P<0.05), which may be associated with the protective effect of GP against I/R-induced renal cell apoptosis. To conclude, the present results suggest that GP produces a protective effect against I/R-induced renal injury as a result of its anti-inflammatory and anti-apoptotic properties.

Effects of paternal cadmium exposure on the sperm quality of male rats and the neurobehavioral system of their offspring.

Cadmium (Cd) is a testicular toxicant and an endocrine disruptor in humans and rodents. The aim of the present study was to investigate the effects of paternal Cd exposure on the sperm quality of male rats and the neurobehavioral system of their offspring. A total of 12 male rats were randomized into a control and Cd-treated group (n=6 per group), and 12 female rats were administered distilled water and randomly divided into two groups (n=6 per group). Subsequently, sperm motility, viability, malformation rate of male rats and the neuromotor maturation, antioxidant ability, Cd accumulation in different organs of their offspring were measured. Compared with the control rats, the sperm motility rate and vitality were significantly reduced (P<0.01) and the sperm malformation rate was significantly increased (P<0.01) in the male rats following Cd treatment. Regarding the nervous system development of the offspring, the cliff-avoidance reflex, surface-righting reflex and negative geotaxis results exhibited significant differences between the Cd exposure and control groups (P<0.05). The Cd content in the liver and heart of the offspring of the Cd exposure rats was higher than that in the control rats (P<0.05), and the liver content peaked on postnatal day 21. Furthermore, Cd exposure affected the antioxidant activity of the offspring, which was shown by glutathione, malondialdehyde and superoxide dismutase assays. Collectively, the results indicate that Cd exposure affects the sperm quality of male rats and the neurobehavioral system of their offspring.

Basal cell carcinoma of the nipple: a case report and review of the literature.

BACKGROUND: The nipple is an extremely unusual location for basal cell carcinoma (BCC). OBJECTIVE: To report a case of BCC originating on the areola and nipple region in a 47-year-old Dominican woman treated with Mohs micrographic surgery (MMS). METHODS: We discuss a case of BCC originating on the areola and nipple region treated with MMS and review the literature regarding treatment of BCC of the nipple. RESULTS: BCCs of the nipple occur rarely, with a total of 19 cases reported in the literature, 6 of which occurred in females. While many of the reported cases were treated with simple excision, several of these required postoperative radiation therapy and/or mastectomy due to their large size and aggressive nature. CONCLUSION: MMS should be considered for treating BCCs at this site as a tissue-sparing measure to minimize deformity of this important anatomic area and to minimize the risk of recurrence.

Dapsone and sulfones in dermatology: overview and update.

In their 60-year history, dapsone and the sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been used successfully to treat a range of dermatologic disorders, most successfully those characterized by abnormal neutrophil and eosinophil accumulation. This article reviews and updates the chemistry, pharmacokinetics, clinical application, mechanism of action, adverse effects, and drug interactions of dapsone and the sulfones in dermatology.

Tazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study.

A double-blind, randomized, vehicle-controlled, parallel-group trial was performed to compare the efficacy and tolerability of tazarotene 0.1% gel and vehicle gel in 31 patients with fingernail psoriasis. Patients were randomized to receive tazarotene or vehicle gel, which they applied each evening for up to 24 weeks to 2 target fingernails, one under occlusion and one unoccluded. The tazarotene treatment resulted in a significantly greater reduction in onycholysis in occluded nails (P < or = .05 at weeks 4 and 12) and a significantly greater reduction in onycholysis in nonoccluded nails (P < or = .05 at week 24). Tazarotene also resulted in a significantly greater reduction in pitting in occluded nails (P < or = .05 at week 24). There were no other significant between-group differences in pitting, subungual hyperkeratosis, leukonychia, nail plate crumbling/loss, splinter hemorrhage, or nail growth rate. Tazarotene 0.1% gel was well tolerated with only 5 of the 21 tazarotene-treated patients reporting a treatment-related adverse event (all mild or moderate). In conclusion, tazarotene 0.1% gel can significantly reduce onycholysis (in occluded and nonoccluded nails) and pitting (in occluded nails) and is well tolerated in the treatment of nail psoriasis.

Preview of potential therapeutic applications of leukotriene B4 inhibitors in dermatology.

This article reviews the mechanisms and potential therapeutic uses of compounds with inhibitory effects on leukotriene B4 (LTB4) production or its activity, and focuses on compounds that have been shown in animal and/or human studies to have potential efficacy in treating dermatological disorders. These compounds, many of which are not familiar to many dermatologists, include inhibitors of 5-lipoxygenase such as ETH615, 15-hydroxyeicosatetraenoic acid, leflunomide, linetastine, lonapalene, MK886, R-68151 and zileuton, and antagonists of LTB4 such as SC53228, SC50605, SC51146 and VML295. The purpose of this paper is to introduce our colleagues to these potentially useful compounds currently in preclinical or early clinical testing.

Altered metabolic response of iron-depleted nonanemic women during a 15-km time trial.

In this double-blinded study, 37 women with iron depletion without anemia (age 19-36 yr) were randomly assigned to receive either an iron supplement (135 mg/day) or a placebo. Endurance capacity was assessed during a 15-km simulated time trial (TT) on a cycle ergometer before and after the 8-wk treatment. After the treatment, although the iron-supplemented group did not have shorter time to finish the TT (time), it had 2.0 kJ/min lower energy expenditure and 5.1% lower fractional utilization of peak oxygen consumption during the TT compared with the placebo group, after controlling for work rate (P < 0.05). Time, fractional utilization of peak oxygen consumption, and plasma lactate concentration at the 5th km of the TT were all negatively associated with hemoglobin levels, after controlling for work rate (P < 0.05). In conclusion, repletion of iron stores to women with iron depletion without anemia increased their energetic efficiency, and oxygen transport capacity of the blood was found to be an important determinant of endurance capacity and energy metabolism in nonanemic women.

Response of serum transferrin receptor to iron supplementation in iron-depleted, nonanemic women.

Serum transferrin receptor (sTfR) concentration has been recognized recently as a reliable indicator of functional iron deficiency, but its response to iron supplementation has not been investigated in marginally iron-deficient women. In this randomized, double-blinded trial, 37 female subjects aged 19-35 y with iron depletion without anemia (hemoglobin > 120 g/L and serum ferritin < 16 microg/L) received an iron supplement or placebo for 8 wk. Iron status was measured before treatment, after 4 wk of treatment, and posttreatment (ie, after 8 wk of treatment). Iron supplementation of these iron-depleted, nonanemic women resulted in a progressive and significant decrease in sTfR and a significant increase in serum ferritin, and prevented a fall in hemoglobin. The responsiveness of sTfR to iron treatment indicated that sTfR is a sensitive indicator of marginal iron deficiency in iron-depleted, nonanemic women, even when their body iron stores were being replenished.

Iron depletion without anemia and physical performance in young women.

Studies in laboratory animals found that iron deficiency without anemia decreased oxidative capacity and increased reliance on carbohydrate as the substrate for energy, thereby causing impaired endurance. The purpose of this cross-sectional study was to investigate the relation between iron deficiency without anemia and physical performance in healthy active women aged 19-36 y. Iron-status assessment included determination of hemoglobin, hematocrit, transferrin saturation, and serum ferritin values. Dietary iron intake was assessed by frequency questionnaires and physical activity level was estimated by frequency questionnaires and 2-wk records. Fifteen women with normal iron status and 15 women with iron depletion (serum ferritin < 12 micrograms/L) were chosen randomly from a group of 69 nonanemic women and given physical-performance tests, including determinations of maximum oxygen consumption (VO2max), ventilatory threshold, and delta-efficiency. There were no significant differences between the two groups in body size, body composition, physical activity level, dietary iron intake, delta-efficiency, or ventilatory threshold. Compared with the iron-depleted group, the iron-sufficient group had significantly higher hemoglobin, transferrin saturation, and serum ferritin values and a significantly greater tendency to use iron supplements. When physical activity level and fat-free mass were controlled for, the iron-depleted group had a significantly lower VO2max. The difference in VO2max was significantly associated with serum ferritin concentration; hemoglobin value was not a significant confounder. Therefore, reduction of VO2max in nonanemic women with iron depletion was likely caused by factors related to reduced body iron storage but was unrelated to decreased oxygen-transport capacity of the blood.

Evidence of a role for fat-free body mass in modulation of plasma carotenoid concentrations in older men: studies with hydrodensitometry.

We examined the relationship between body composition and changes in plasma carotenoid concentration in response to dietary carotenoid restriction or beta-carotene (betaC) supplementation in healthy older men. Subjects (mean age 65 y) were assigned randomly to supplement (30 mg betaC/d) or placebo groups, and all subjects consumed a standard low carotenoid basal diet plus 1.5 mg betaC/d as carrots. Body composition was measured at baseline by hydrodensitometry, and plasma carotenoids were measured at baseline and after 28 d of treatment by HPLC. Baseline plasma total carotenoid concentration was significantly and negatively correlated with body mass index (BMI) and fat-free mass (FFM) but not with fat mass, whereas baseline betaC concentration was negatively associated with all three variables. The increase in plasma betaC concentration in response to betaC supplementation was significantly and inversely correlated with BMI and FFM but not with fat mass. Likewise, the decline in plasma total carotenoid concentration in the placebo group was also significantly and inversely related to BMI and FFM but not to fat mass. Thus, FFM seems to be an important determinant of plasma carotenoid concentrations and to explain a substantial portion of the often-observed relationship between BMI and blood carotenoid levels. Fat-free mass seems to represent a dynamic reservoir that dampens short-term changes in plasma carotenoid concentrations during fluctuation in carotenoid intake.