Developmental programming: intrauterine caloric restriction promotes upregulation of mitochondrial sirtuin with mild effects on oxidative parameters in the ovaries and testes of offspring.

According to the developmental origins of health and disease (DOHaD) hypothesis, changes in the maternal environment are known to reprogram the metabolic response of offspring. Known for its redox modulation, caloric restriction extends the lifespan of some species, which contributes to diminished cellular damage. Little is known about the effects of gestational caloric restriction, in terms of antioxidant parameters and molecular mechanisms of action, on the reproductive organs of offspring. This study assessed the effects of moderate (20%) caloric restriction on redox status parameters, molecular expression of sirtuin (SIRT) 1 and SIRT3 and histopathological markers in the ovaries and testes of adult rats that were subjected to gestational caloric restriction. Although enzyme activity was increased, ovaries from female pups contained high levels of oxidants, whereas testes from male pups had decreased antioxidant enzyme defences, as evidenced by diminished glyoxalase I activity and reduced glutathione content. Expression of SIRT3, a deacetylase enzyme related to cellular bioenergetics, was increased in both ovaries and testes. Previous studies have suggested that, in ovaries, diminished antioxidant metabolism can lead to premature ovarian failure. Unfortunately, there is little information regarding the redox profile in the testis. This study is the first to assess the redox network in both ovaries and testes, suggesting that, although intrauterine caloric restriction improves molecular mechanisms, it has a negative effect on the antioxidant network and redox status of reproductive organs of young adult rats.

Shock-Wave Therapy Improves Myocardial Blood Flow Reserve in Patients with Refractory Angina: Evaluation by Real-Time Myocardial Perfusion Echocardiography.

BACKGROUND: Cardiac shock-wave therapy (CSWT) has been demonstrated as an option for the treatment of patients with refractory angina (RA), promoting immediate vasodilatory effects and, in the long-term, neoangiogenic effects that would be responsible for reducing the myocardial ischemic load. The aim of this study was to determine the effects of CSWT on myocardial blood flow reserve (MBFR) assessed by quantitative real-time myocardial perfusion echocardiography in patients with RA. METHODS: Fifteen patients (mean age 61.5 ± 12.8 years) with RA who underwent CSWT during nine sessions, over 3 months of treatment, were prospectively studied. A total of 32 myocardial segments with ischemia were treated, while another 31 did not receive therapy because of technical limitations. Myocardial perfusion was evaluated at rest and after dipyridamole stress (0.84 mg/kg) before and 6 months after CSWT, using quantitative real-time myocardial perfusion echocardiography. Clinical effects were evaluated using Canadian Cardiovascular Society grading of angina and the Seattle Angina Questionnaire. RESULTS: The ischemic segments treated with CSWT had increased MBFR (from 1.33 ± 0.22 to 1.74 ± 0.29, P < .001), a benefit that was not observed in untreated ischemic segments (1.51 ± 0.29 vs 1.54 ± 0.28, P = .47). Patients demonstrated increased global MBFR (from 1.78 ± 0.54 to 1.89 ± 0.49, P = .017). Semiquantitative single-photon emission computed tomographic analysis of the treated ischemic segments revealed a score reduction from 2.10 ± 0.87 to 1.68 ± 1.19 (P = .024). There was improvement in Canadian Cardiovascular Society score (from 3.20 ± 0.56 to 1.93 ± 0.70, P < .05) and in Seattle Angina Questionnaire score (from 42.3 ± 12.99 to 71.2 ± 14.29, P < .05). No major cardiovascular events were recorded during follow-up. CONCLUSIONS: CSWT improved MBFR in ischemic segments, as demonstrated by quantitative real-time myocardial perfusion echocardiography. These results suggest that CSWT has the potential to increase myocardial blood flow, with an impact on symptoms and quality of life in patients with RA.

Cardiac shock wave therapy improves myocardial perfusion and preserves left ventricular mechanics in patients with refractory angina: A study with speckle tracking echocardiography.

BACKGROUND: Cardiac shockwave therapy (CSWT) is a new potential option for the treatment of patients with chronic coronary disease and refractory angina (RA). We aimed to study the effects of CSWT on left ventricular myocardial perfusion and mechanics in patients with RA. METHOD: We prospectively studied 19 patients who underwent CSWT. Left ventricular mechanics were evaluated by speckle tracking echocardiography (STE), and myocardial perfusion by single-photon emission computed tomography, using stress/rest-Technetium-99 m Sestamibi, for determination of summed stress score (SSS). Canadian Cardiac Society (CCS), New York Heart Association (NYHA), and quality of life by Seattle Angina Questionnaire (SAQ) were assessed at baseline and 6 months after therapy. RESULTS: CSWT therapy was applied without major side effects. At baseline, 18 patients (94.7%) had CCS class III or IV, and after CSWT there was reduction to 3 (15.8%), P = .0001, associated with improvement in SAQ (38.5%; P < .001). Thirteen (68.4%) had class NYHA III or IV before treatment, with significant reduction to 7 (36.8%); P = .014. No change was observed in the global SSS from baseline to 6-month follow-up (15.33 ± 8.60 vs 16.60 ± 8.06; P = .157). However, there was a significant reduction in the average SSS of the treated ischemic segments (2.1 ± 0.87 pre vs 1.6 ± 1.19 post CSWT; P = .024). Global longitudinal strain by STE remained unaltered (-13.03 ± 8.96 pre vs -15.88 ± 3.43 6-month post CSWT; P = .256). CONCLUSION: CSWT is a safe procedure for the treatment of patients with RA that results in better quality of life, improvement in myocardial perfusion of the treated segments with preservation of left ventricular mechanics.

The protective role of fucosylated chondroitin sulfate, a distinct glycosaminoglycan, in a murine model of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Heparanase-1 activation, albuminuria, and a decrease in glomerular heparan sulfate (HS) have been described in diabetic nephropathy (DN). Glycosaminoglycan (GAG)-based drugs have been shown to have renoprotective effects in this setting, although recent trials have questioned their clinical effectiveness. Here, we describe the effects of fucosylated chondroitin sulfate (FCS), a novel GAG extracted from a marine echinoderm, in experimentally induced DN compared to a widely used GAG, enoxaparin (ENX). METHODS: Diabetes mellitus (DM) was induced by streptozotocin in male Wistar rats divided into three groups: DM (without treatment), FCS (8 mg/kg), and ENX (4 mg/kg), administered subcutaneously. After 12 weeks, we measured blood glucose, blood pressure, albuminuria, and renal function. The kidneys were evaluated for mesangial expansion and collagen content. Immunohistochemical quantifications of macrophages, TGF-ß, nestin and immunofluorescence analysis of heparanase-1 and glomerular basement membrane (GBM) HS content was also performed. Gene expression of proteoglycan core proteins and enzymes involved in GAG assembly/degradation were analyzed by TaqMan real-time PCR. RESULTS: Treatment with GAGs prevented albuminuria and did not affect the glucose level or other functional aspects. The DM group exhibited increased mesangial matrix deposition and tubulointerstitial expansion, and prevention was observed in both GAG groups. TGF-ß expression and macrophage infiltration were prevented by the GAG treatments, and podocyte damage was halted. The diabetic milieu resulted in the down-regulation of agrin, perlecan and collagen XVIII mRNAs, along with the expression of enzymes involved in GAG biosynthesis. Treatment with FCS and ENX positively modulated such changes. Heparanase-1 expression was significantly reduced after GAG treatment without affecting the GBM HS content, which was uniformly reduced in all of the diabetic animals. CONCLUSIONS: Our results demonstrate that the administration of FCS prevented several pathological features of ND in rats. This finding should stimulate further research on GAG treatment for this complication of diabetes.

Recalcitrant molluscum contagiosum in a patient with AIDS: combined treatment with CO(2) laser, trichloroacetic acid, and pulsed dye laser.

BACKGROUND AND OBJECTIVE: Recalcitrant molluscum contagiosum (MC) in patients with acquired immunodeficiency syndrome (AIDS) is usually difficult to treat. We present a case treated by a combination of CO(2) laser, trichloroacetic acid, and the 585-nm pulsed dye laser (PDL). The purpose was to determine the effectiveness and ease of these treatment modalities. STUDY DESIGN/MATERIALS AND METHODS: A patient with AIDS presented with recalcitrant MC lesions, predominantly located on the face. The lesions were first treated with the CO(2) laser, in two sessions. Recurrent lesions were treated either with 50% trichloroacetic acid (TCA) or with the PDL. RESULTS: The CO(2) laser treated lesions healed within 2 weeks without secondary infection. The PDL and the TCA treated lesions resolved completely after one treatment. CONCLUSION: Treatment of MC in AIDS patients remains a challenge. The combination of two or more therapeutic modalities, such as CO(2) laser, PDL, and TCA can be of great help to improve the quality of life of these patients.