Nogo receptor antagonizes p75NTR-dependent motor neuron death

The Nogo-66 receptor (NgR) plays a critical role in restricting axon regeneration in the central nervous system. This inhibitory action is in part mediated by a neuronal receptor complex containing p75NTR, a multifunctional receptor also well known to trigger cell death upon binding to neurotrophins such as NGF. In the present study, we show that Pep4 and NEP1-40, which are two peptides derived from the Nogo-66 sequence that modulate NgR-mediated neurite outgrowth inhibition, prevent NGF-stimulated p75NTR-dependent death of cultured embryonic motor neurons. They also confer protection on spinal cord motor neurons after neonatal sciatic nerve axotomy. These findings demonstrate an as-yet-unknown function of NgR in maintaining neuronal survival that may be relevant for motor neuron development and degeneration.     

Upgrade Recycling of Cast Iron Scrap Chips towards β-FeSi2 Thermoelectric Materials

The upgrade recycling of cast-iron scrap chips towards β-FeSi₂ thermoelectric materials is proposed as an eco-friendly and cost-effective production process. By using scrap waste from the machining process of cast-iron components, the material cost to fabricate β-FeSi₂ is reduced and the industrial waste is recycled. In this study, β-FeSi₂ specimens obtained from cast iron scrap chips were prepared both in the undoped form and doped with Al and Co elements. The maximum figure of merit (ZT) indicated a thermoelectric performance of approximately 70% in p-type samples and nearly 90% in n-type samples compared to β-FeSi₂ prepared from pure Fe and other published studies. The use of cast iron scrap chips to produce β-FeSi₂ shows promise as an eco-friendly and cost-effective production process for thermoelectric materials.     

Case Report: Trypanosoma cruzi Meningoencephalitis in a Patient with Acquired Immunodeficiency Syndrome

As a result of global migration, a significant number of people with Trypanosoma cruzi infection now live in the United States, Canada, many countries in Europe, and other non-endemic countries. Trypanosoma cruzi meningoencephalitis is a rare cause of ring-enhancing lesions in patients with acquired immunodeficiency syndrome (AIDS) that can closely mimic central nervous system (CNS) toxoplasmosis. We report a case of CNS Chagas reactivation in an AIDS patient successfully treated with benznidazole and antiretroviral therapy in the United States.Trypanosoma cruzi meningoencephalitis is a rare cause of ring-enhancing lesions in patients with acquired immunodeficiency syndrome (AIDS) that can closely mimic central nervous system (CNS) toxoplasmosis. Diagnosis is often delayed and mortality is 79–100% despite treatment^1,2; to our knowledge, only four cases of T. cruzi meningoencephalitis in human immunodeficiency virus (HIV)-infected patients have been reported in the United States.^3–6 None of the four patients have survived. We report a case of CNS Chagas reactivation in an AIDS patient successfully treated with benznidazole and antiretroviral therapy in the United States.A 49-year-old right-handed woman originally from Honduras was admitted to our hospital with a 3-week history of progressive altered mental status, headache, and right-sided weakness. On the day of symptom onset, she presented to an outside hospital and magnetic resonance imaging (MRI) of the brain revealed two ring-enhancing lesions associated with edema. She was also diagnosed with AIDS (CD4 count of 38 cells/μL and an HIV viral load of 375,000 copies/mL). The patient underwent an MRI-guided biopsy of the left parietal lesion and was diagnosed with cerebral Toxoplasmosis. After 14-days, she was discharged to continue treatment of cerebral toxoplasmosis with sulfadiazine and pyrimethamine; however, she was nonadherent with her medications.On admission to our hospital, she was afebrile and physical examination was notable for altered mental status and weakness of the right upper and lower extremities (3/5, Medical Research Council scale) without sensory deficit. The MRI of the brain showed worsening ring-enhancing lesions within the right superior frontal gyrus (1.4 × 1.2 cm) and left parietal lobe (2.4 × 2.2 cm) with moderate vasogenic edema and regional mass effect and adjacent leptomeningeal enhancement. She was started on oral sulfadiazine, pyrimethamine, and glucocorticosteroids. On hospital Day 5, the patient had worsening mental status and a computed tomography of the head showed enlargement of the right frontal lesion with increased edema. A lumbar puncture was performed. Cerebrospinal fluid (CSF) contained three white blood cells/μL and one red blood cell/μL. The CSF protein was 78 mg/dL and glucose was 55 mg/dL. The CSF Gram stain was negative for bacteria but Wright-Giemsa stain revealed numerous flagellated parasites consistent with T. cruzi trypomastigotes (Figure 1). Fungal and acid fast bacilli stain and cultures and CSF cryptococcal antigen were negative. Serologic studies were negative for Toxoplasma IgG and IgM but positive for T. cruzi antibody by the indirect fluorescent antibody test and enzyme immunoassay. The CSF and serum polymerase chain reaction studies were positive for T. cruzi and negative for Toxoplasma. Electrocardiogram and transthoracic echocardiogram were negative for findings to suggest Chagas cardiomyopathy.Open in a separate windowFigure 1.Trypanosoma cruzi trypomastigotes in cerebrospinal fluid (CSF) (Giemsa stain, ×1,000).The brain biopsy histopathology slides were obtained from an outside hospital, which revealed numerous intracellular organisms with rod-shaped kinetoplast, consistent with T. cruzi amastigotes (Figure 2).Open in a separate windowFigure 2.Trypanosoma cruzi amastigotes with rod-shaped kinetoplasts in glial cells (Giemsa stain, ×1,000).Treatment with benznidazole 5 mg/kg/day was started for Chagasic meningoencephalitis and brain abscesses. Her mental status improved gradually, although her right-sided weakness remained unchanged. Antiretroviral therapy was started 17 days after initiation of antitrypanosomal therapy. Repeat MRI of the brain 2 weeks after treatment showed a decrease in the size of the two lesions and surrounding edema. She completed a 60-day induction therapy. At last follow-up 5 months after initial diagnosis, she was clinically stable without evidence of recurrence and her CD4 count was 359 cells/μL with HIV viral load of 162 copies/ml.Chagas disease, or American trypanosomiasis, is estimated to affect ∼8–10 million people in the world, primarily in Latin America and the Caribbean.^7,8 As a result of global migration, a significant number of people with T. cruzi infection now live in the United States, Canada, many countries in Europe, and other non-endemic countries.⁹ In the United States alone, it is estimated that ∼0.3 to 1 million people are infected with T. cruzi.¹⁰Reactivation of chronic T. cruzi infection can occur in immunosuppressed patients such as those with hematologic malignancies, organ transplantation, and AIDS. In Chagas-endemic countries, T. cruzi and HIV coinfection rate ranges from 1.3% to 7.1%.¹¹ Although the chronic phase of Chagas disease in non-immunosuppressed patients most commonly manifests as cardiac disease or gastrointestinal dysfunction, the most common manifestations of T. cruzi reactivation in patients with AIDS are CNS lesions and menigoencephalitis. Most of the reported cases have occurred in HIV-infected patients with a CD4 count < 200 cells/μL.^1,2,12 T. cruzi reactivation in patients with AIDS can closely mimic cerebral toxoplasmosis clinically and radiographically, thus patients are often misdiagnosed resulting in a delay in appropriate treatment.¹²Identification of T. cruzi trypomastigote in CSF is diagnostic of chagasic encephalitis. However, a negative CSF smear does not rule out the disease. In a report of 15 cases from Argentina, CSF direct examination for T. cruzi was positive in 11 of 13 patients.² A brain biopsy may be necessary when the diagnosis remains unclear. The recommended treatment of CNS Chagas reactivation in HIV patients is benznidazole 5 mg/kg daily divided into two doses for 60–90 days and some authors recommend secondary prophylaxis with benznidazole 5 mg/kg three times per week.¹² Nifurtimox is considered an alternative treatment but clinical experience is limited. Immune reconstitution with highly active antiretroviral therapy likely plays an important role in the control of Chagas reactivation but optimal timing for initiation of antiretroviral therapy remains unclear.¹² Chagasic menigoencephalitis should be considered in HIV-infected patients with CNS lesions who are from T. cruzi-endemic areas.     

La super hypertension artérielle en milieu cardiologique au Burkina Faso

Super hypertension is defined as systolic BP ≥ 250 mmHg and/or diastolic BP ≥ 150 mmHg in presence or not of complications. The aim of our study was to describe the epidemiological and evolutive patterns of super hypertension in the cardiology department of the Yalgado Ouedraogo University Hospital. It was an observation cohort over a period of 26 months (July 2011 to August 2013). We recruited 34 patients, corresponding to a prevalence of 12.9% of all hypertensive patients. The median time of follow-up was 7.1 months. The mean age was 47 years old, with a sex-ratio of 1.3. Twenty-one (62%) of the patients were known hypertensive, out of who 24% were regularly rewiewed, 57% on treatment, but none was on regular medications. Dyspnoea was the reason for consulting in 38% of the cases. We noticed a fundoscopy stage III or IV in 55.9% of the cases. All patients had left ventricular hypertrophy on ECG, and 90% on echocardiography. Complication was noticed on admission in 91% of the cases. Chronic renal failure occured in 14.7% of the cases during follow-up, and overall mortality rate was 0.5 person years. Probability of survival over one month was 70% for all patients. The mean age of deceased was 35%. Presence of renal failure, unknown hypertension, and age < 45 were factors linked to death (P < 0.05). Super hypertension is a pathology of the youth, with high morbi-mortality. The prevention is done through early detection and efficient management of hypertension.     

Case Report: Cutaneous Leishmaniasis in Cuban Immigrants to Texas who Traveled through the Darién Jungle,Panama

Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis.Leishmaniasis is a vector-borne disease caused by the protozoan parasite of the genus Leishmania and is spread by the bite of sand flies from the sub-family Phlebotominae.¹ There are various clinical manifestations of leishmaniasis, including cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis, and visceral leishmaniasis. Cutaneous leishmaniasis occurs at the site of the bite, with lesions forming weeks to months later starting with a papule, which then develops into a nodule or plaque-like lesion and progresses to a painless ulceration with an indurated border.We report four cases of CL caused by Leishmania (Viannia) panamensis in Cuban immigrants who traveled through the Darién Gap Jungle between Colombia and Panama on their journey north to the United States. This region has been shown to have high transmission rates of leishmaniasis,² and, in 2012, Panama experienced an outbreak beyond expected endemic rates.³ This case series highlights a previously underappreciated immigration route to the United States for Cubans and the need to include leishmaniasis as a differential diagnosis for non-healing skin ulcers in this patient population.During May 2012–April 2013, four persons who had recently immigrated to the United States from Cuba came to the National School of Tropical Medicine at Baylor College of Medicine''s (BCM) Tropical Medicine Clinic for non-healing skin ulcers. All four persons reported a similar route of travel from Cuba to Texas (Figure 1), although at different times. Each person began their journey by flying to Quito, Ecuador, where they then traveled by bus through Colombia, passing through the cities of Pasto and Cali to Quibdo. In Quibdo, they took a short flight to Bahia Solano, Colombia, where a boat ride then transported them to Punta Ardita near the Panama border. They then traveled by foot through the thick jungle in Darién, Panama, for 5–15 days. During this time, they slept outdoors and reported numerous insect bites. Once through the Darién area, they traveled northward until they entered the United States at the Mexican border.Open in a separate windowFigure 1.Map showing immigration route of a cluster of Cuban patients with cutaneous leishmaniasis caused by Leishmania (V.) panamensis. Note the travel by foot through the thick jungle of the Darién National Park, Panama, where they likely contracted the disease.Once in the United States, the four persons sought medical care at outside clinics for skin lesions that had developed within two months after they passed though the Darién. They were treated for presumed infection with Staphylococcus aureus. The antibiotics had no therapeutic effect, and the lesions continued to grow and develop into non-healing, painless ulcers with accompanying satellite lesions. Once in Houston, Texas, the four persons were directed to the Department of Dermatology at BCM (

Mitigation of acetamiprid – induced renotoxicity by natural antioxidants via the regulation of ICAM,NF-kB and TLR 4 pathways

BackgroundAcetamiprid (ACMP) is a member of the neonicotinoid group of insecticides. It is extensively used worldwide. The misuse of ACMP creates danger hazards to human and animal.MethodsACMP induced renal damage evidenced by an increase in kidney injury biomarkers. So the goal of this work is to clarify the reno protective effect of Quercetin (Qrctn) and/or Nano-glutathione (N-Gluta) solely or in combination to counterbalance the danger effect of ACMP. All treatments with the previous agents were coadministered orally with ACMP for one month.ResultsACMP ingestion caused a significant rise in serum creatinin, urea, and uric acid, TNF α along with renal cystatin C, lipid peroxidation and nitric oxide with the concomitant decline in the levels of reduced glutathione and IL-10 levels. Protein expression of ICAM was upregulated as well as mRNA expression of NF-κB while mRNA expression of Nrf2 was down-regulated. Immune histochemistry of TLR 4 revealed strong immune reaction. The administration of Qrctn or N-Gluta either individually or together modulated all the preceding aforementioned parameters.ConclusionFascinatingly Qrctn and N-Gluta combination was the most powerful regimen to frustrate ACMP reno-toxicity and may be deliberate as a hopeful applicant for renal therapy.