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.     

Desarrollo y validación de la versión abreviada del Transsexual Voice Questionnaire for Male-to-Female Transsexuals en español

ObjectiveThe aim of this study was to create and validate an abbreviated version of the Spanish Transsexual Voice Questionnaire for Male-to-Female Transsexuals (SvTVQ^MtF).SettingThe study was conducted by two referral hospitals for voice feminization surgery and by a university department of psychology and speech therapy, all in Spain.Subjects and methodsWe prospectively studied 51 male-to-female transsexuals who underwent voice feminization surgery between January 2017 and December 2018. The SvTVQ^MtF was completed before and after surgery, and the 10 items with the greatest variation were selected by clinical consensus of an expert panel to develop the short version of the SvTVQ^MtF (SvTVQ^MtF-10). The correlation between the total score and the score for each item on the SvTVQ^MtF and the SvTVQMtF-10 was studied. The internal consistency of the SvTVQ^MtF-10 was analysed.ResultsGood correlation (Pearson coefficient above .90) was found between the two questionnaires. A significant correlation was found between the total SvTVQ^MtF-10 score and the score for each item. A significant negative correlation was found between the SvTVQ^MtF and fundamental frequency after voice feminization surgery. Cronbach's α was .79.ConclusionThe SvTVQ^MtF-10 is a valid short version of the SvTVQ^MtF and can be used to quantify voice-related quality of life in MtF transsexuals.     

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients

The Cerebellum - The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are...     

Absceso retrofaríngeo. Revisión clínica de veinticinco años

IntroductionRetropharyngeal abscess is a serious condition. Its rare occurrence, thus sharing symptoms with other processes, make it a diagnostic challenge for the clinician. Therefore, it is critical to make an early diagnosis to prevent delaying treatment and avoid complications.ObjectivesTo gain knowledge of the epidemiology, pathogenesis, clinical manifestations, the most commonly implicated microorganisms, the type of treatment used, morbidity and mortality of retropharyngeal abscesses at a tertiary institution over the last 25 years.MethodsA retrospective study was conducted by reviewing medical records of all patients diagnosed with retropharyngeal abscess in a single centre between 1 January 1990 and 31 February 2016. Thirty-three patients were included in our study. Data such as personal history, present illness, diagnoses and treatment procedures were collected from the medical records.ResultsThe incidence during the years of study was 0.2 cases/100 000 inhabitants/year. Personal medical histories most often associated were alcoholism, smoking, diabetes and obesity. The most common aetiology found was impaction of a foreign body (especially fishbone). The most common presenting symptoms were odynophagia and neck pain accompanied by fever. Preventive tracheotomy was performed in the initial management of the patient in 9 cases (27%). The most frequent complication was descending necrotizing mediastinitis. Surgical drainage of the abscess was required in 27 patients (82%), especially with external approaches (17 cases). Two patients had sequelae: paralysis of unilateral vocal cord and Horner's syndrome. No mortality was observed in the patients of the study.ConclusionRetropharyngeal abscesses must be considered medical-surgical emergencies as they are likely to produce serious complications. We must pay attention to the warning symptoms such as odynophagia and cervical pain, associated or otherwise with dyspnoea, stridor, trismus, and neck stiffness. Advances in diagnostic and therapeutic procedures together with advances in critical care have been a key factor in improving the prognosis and mortality of these patients.     

Hemangioma with dabskoid features: a rare histopathologic variant of acquired hemangioma

Dabska tumor, also known as papillary intralymphatic angioendothelioma (PILA), is a locally aggressive hemangiendothelioma characterized by intravascular papillary proliferations of atypical endothelial cells. Besides PILA, papillary tufts lined by hobnail endothelial cells have been rarely described in vascular proliferations. We report two cases of acquired hemangiomas, which focally showed this finding. We present a 15‐year‐old male and a 7‐year‐old girl with erythematous nodules. Both lesions were composed of capillary lobules intermingled with large sinusoidal spaces lined with a single layer of flat endothelial cells, which focally developed intravascular papillary proliferations lined by plump hyperchromatic endothelial cells and a central connective tissue core. Both types of cells were positive with CD31 and ERG and negative for Lyve‐1, Prox‐1 and podoplanin. Wilm's tumor 1 marker was strongly positive in the capillary hemangioma areas while negative in the intravascular tufts. Both lesions recurred after the first excision but we did not observe further recurrence or evidence of metastasis in the follow‐up. In summary, our cases expand the histopathologic findings that may be seen in conventional acquired capillary hemangiomas. The focal presence of dabskoid tufts within an otherwise conventional capillary hemangioma should be not misinterpreted as evidence of malignancy.     

In vitro activity of beta-lactam and non-beta-lactam antibiotics in extended-spectrum beta-lactamase-producing clinical isolates of Escherichia coli

The activity of different beta-lactam and non-beta-lactam antibiotics was assessed against extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing clinical isolates of Escherichia coli. A phenotypic study to discover the presence of ESBLs in 399 clinical isolates of E. coli was made by the disk diffusion method following the Clinical and Laboratory Standards Institute (formely NCCLS, 2004) guidelines. The activity of different antibiotics was subsequently studied using the automated VITEK 2 system (bioMérieux, Marcy l'Etoile, France). One hundred fifteen isolates proved to be ESBL-producing and 284 non-ESBL-producing. Among the former, percentage susceptibilities to the antibiotics assayed were meropenem and amikacin, 100%; piperacillin/tazobactam, 97.4%; cefepime, 94.8%; amoxicillin/clavulanic acid, 84.3%; tobramycin, 84.3%; gentamicin, 83.5%; cefoxitin, 83.5%; nitrofurantoin, 71.3%; cotrimoxazole, 46.1%; norfloxacin, 29.6%; ciprofloxacin, 27%; and ofloxacin, 26.1%.     

FM19G11 reverses endothelial dysfunction in rat and human arteries through stimulation of the PI3K/Akt/eNOS pathway,independently of mTOR/HIF-1α activation

Background and Purpose

FM19G11 up-regulates mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α) and PI3K/Akt pathways, which are involved in endothelial function. We evaluated the effects of FM19G11 on defective endothelial vasodilatation in arteries from rats and humans and investigated the mechanisms involved.

Experimental Approach

Effects of chronic in vivo administration of FM19G11 on aortic endothelial vasodilatation were evaluated together with ex vivo treatment in aortic and mesenteric arteries from control and insulin-resistant rats (IRR). Its effects on vasodilator responses of penile arteries (HPRAs) and corpus cavernosum (HCC) from men with vasculogenic erectile dysfunction (ED) (model of human endothelial dysfunction) were also evaluated. Vascular expression of phosphorylated-endothelial NOS (p-eNOS), phosphorylated-Akt (p-Akt) and HIF-1α was determined by immunodetection and cGMP by elisa.

Key Results

Chronic administration of FM19G11 reversed the impaired endothelial vasodilatation in IRR. Ex vivo treatment with FM19G11 also significantly improved endothelium-dependent vasodilatation in aorta and mesenteric arteries from IRR. These effects were accompanied by the restoration of p-eNOS and cGMP levels in IRR aorta and were prevented by either NOS or PI3K inhibition. p-Akt and p-eNOS contents were increased by FM19G11 in aortic endothelium of IRR. FM19G11-induced restoration of endothelial vasodilatation was unaffected by mTOR/HIF-1α inhibitors. FM19G11 also restored endothelial vasodilatation in HPRA and HCC from ED patients.

Conclusions and Implications

Stimulation of the PI3K/Akt/eNOS pathway by FM19G11 alleviates impaired NO-mediated endothelial vasodilatation in rat and human arteries independently of mTOR/HIF-1α activation. This pharmacological strategy could be beneficial for managing pathological conditions associated with endothelial dysfunction, such as ED.     

The natural history of nonalcoholic fatty liver disease: a population-based cohort study

BACKGROUND & AIMS: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver-related morbidity among community-based NAFLD patients. METHODS: Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. RESULTS: Mean (SD) age at diagnosis was 49 (15) years; 231 (49%) were male. Mean follow-up was 7.6 (4.0) years (range, 0.1-23.5) culminating in 3192 person-years follow-up. Overall, 53 of 420 (12.6%) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003-1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7-2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3-5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2-7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7%) subjects. Twenty-one (5%) patients were diagnosed with cirrhosis, and 13 (3.1%) developed liver-related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. CONCLUSIONS: Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver-related death is a leading cause of mortality, although the absolute risk is low.