Epigallocatechin Gallate Mitigates the Methamphetamine-Induced Striatal Dopamine Terminal Toxicity by Preventing Oxidative Stress in the Mouse Brain

Methamphetamine (METH) is a popular psychostimulant due to its long-lasting effects and inexpensive production. METH intoxication is known to increase oxidative stress leading to neuronal damage. Thus, preventing the METH-induced oxidative stress can potentially mitigate neuronal damage. Previously, our laboratory found that epigallocatechin gallate (EGCG), a strong antioxidant found in green tea, can protect against the METH-induced apoptosis and dopamine terminal toxicity in the striatum of mice. In the present study, we evaluated the anti-oxidative properties of EGCG on the METH-induced oxidative stress using CD-1 mice. First, we demonstrated that mice pretreated with EGCG 30 min prior to the METH injection (30 mg/kg, ip) showed protection against the striatal METH-induced reduction of tyrosine hydroxylase without mitigating hyperthermia. In addition, injecting a single high dose of METH caused the reduction of striatal glutathione peroxidase activity at 24 h after the METH injection. Interestingly, pretreatment with EGCG 30 min prior to the METH injection prevented the METH-induced reduction of glutathione peroxidase activity. Moreover, we utilized Western blots to quantify the glutathione peroxidase 4 protein level in the striatum. The results showed that METH decreased striatal glutathione peroxidase 4 protein level, and the reduction was prevented by EGCG pretreatment. Finally, we observed that the METH-induced increase of striatal catalase and copper/zinc superoxide dismutase protein levels were also attenuated by pretreatment with EGCG. Taken together, our data indicate that EGCG is an effective agent that can be used to mitigate the METH-induced striatal toxicity in the mouse brain.     

Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial

Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34⁺ and CD34⁺KDR⁺ progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p < 0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21–1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41–19.5, p < 0.02). Baseline CD34⁺KDR⁺ were higher in rs753482AA (166.2 ± 154.0 × 10⁶ events) than in rs753482AC+CC (63.1 ± 26.9 × 10⁶ events, p < 0.01). At the end of the study, the highest circulating CD34⁺KDR⁺ were found in IIT rs753482AA (246.9 ± 194.0 × 10⁶ events) while the lowest levels were found in SC rs753482AC+CC (70.9 ± 45.0 × 10⁶ events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.     

Sexual Function after Modified Radical Hysterectomy (Piver II/Type B) vs. Classic Radical Hysterectomy (Piver III/Type C2) for Early Stage Cervical Cancer. A Prospective Study

IntroductionWhen cervical cancer is detected at an early stage (International Federation of Gynecology and Obstetrics [FIGO] IA2‐IB1), it can be successfully treated by radical surgery alone. Considering that most patients are young and sexually active at the moment of diagnosis and the long life expectancy of survivors after the treatment, quality of life (QoL) and sexual function are important issues for cancer survivors and caregivers. However, only a few studies have examined the QoL and sexual function in disease‐free cervical cancer survivors, and there are no studies in the literature comparing prospectively sexual function after different types of radical hysterectomy.AimTo compare sexual function in two groups of early stage cervical cancer survivors treated by radical surgery alone, undergoing two different types of radical hysterectomy.MethodsPatients treated by radical hysterectomy with systematic lymphadenectomy for early stage cervical cancer (FIGO IA2‐IB1) have been enrolled and divided in two groups with regard to type of radical hysterectomy performed; S1: modified radical hysterectomy (Piver II/Type B), S2: classic radical hysterectomy (Piver III/ Type C2).Main Outcome MeasureTwenty‐four months after surgery we assessed the sexual function using the European Organization for Research and Treatment of Cancer Cervix Cancer Module Questionnaire, which is a validated system for the assessment of disease‐ and treatment‐specific issues that affect the QoL and sexual functioning of women who are treated for cervical cancer.ResultsOf the 31 patients enrolled in the S1 group and 46 in the S2 group, 23 and 33 patients have been included, respectively. We observed significant differences between the two groups in terms of symptom experience, sexual/vaginal functioning, sexual activity, and sexual enjoyment. There was not any significant difference regarding lymphedema, peripheral neuropathy, and sexual worry.ConclusionSurvivors of early stage cervical cancer treated by modified radical hysterectomy (Piver II/ Type B) have a better sexual function than those operated by classic radical hysterectomy (Piver III/ Type C2). Plotti F, Nelaj E, Sansone M, Antonelli E, Altavilla T, Angioli R, and Benedetti Panici P. Sexual function after modified radical hysterectomy (Piver II/Type B) vs. classic radical hysterectomy (Piver III/Type C2) for early stage cervical cancer: A prospective study. J Sex Med 2012;9:909–917.     

Clinical use of the perifollicular vascularity assessment in IVF cycles: a pilot study

BACKGROUND: In Italy, a recent law has imposed a ban on the fertilization of more than three oocytes at one time, and all resulting embryos produced must be transferred simultaneously. The aim of the present controlled study was to assess the clinical feasibility and efficacy of the perifollicular vascularity assessment for oocyte selection in IVF cycles. METHODS: Fifty-four young primary infertile non-obese women (27 cases and 27 age- and BMI-matched controls) underwent IVF cycles. The choice of the oocytes to fertilize was performed according to perifollicular vascularization in the experimental group, whereas in the control group, the standard morphologic criteria alone were used. The dose of gonadotrophins used, the dominant follicles obtained, the duration of the ovarian stimulation, the number of oocytes retrieved, the number/quality of oocytes fertilized and of cleaved embryos, cycle cancellation, implantation, clinical pregnancy, ongoing pregnancy, multiple pregnancies and ovarian hyperstimulation syndrome rates were assessed in each group. RESULTS: The assessment of perifollicular vascularity was feasible in 88.9% of cases. No difference between groups was detected in any parameter evaluated. CONCLUSION: Power Doppler assessment of perifollicular vascularity seems to have no clinical utility for oocyte selection in IVF cycles for young infertile women.     

Safe wrapping of the borderline dilated ascending aorta during aortic valve replacement

Background  

Techniques of reduction aortoplasty are widely published in the literature with conflicting results. External support seems to be an important factor in preventing recurrence but, in some cases, this technique caused erosion of the aorta because of the wrinkles the prosthesis creates in the rear side of the aorta.     

ERI1: A case report of an autosomal recessive syndrome associated with developmental delay and distal limb abnormalities

ERI1 is an evolutionary conserved 3′–5′ exonuclease with an important function in multiple RNA processing pathways. Although the molecular mechanisms in which ERI1 is involved have been studied extensively in model organisms, the pathology associated with ERI1 variants in humans has remained elusive because no case has been reported so far. Here, we present a case of a female patient with a homozygous nonsense variant in ERI1 gene. The patient exhibits mild intellectual disability, eyelid ptosis, and anomalies in her hands and feet (brachydactyly, clinodactyly, dysplastic/short nail of halluces, brachytelephalangy, short metacarpals, and toe syndactyly). This case report is the first of its kind and is invaluable for understanding ERI1 pathology in humans.