TNF receptor I sensitizes neurons to erythropoietin- and VEGF-mediated neuroprotection after ischemic and excitotoxic injury

CNS neurons use robust cytoprotective mechanisms to ensure survival and functioning under conditions of injury. These involve pathways induced by endogenous neuroprotective cytokines such as erythropoietin (EPO). Recently, in contrast to its well known deleterious roles, TNF has also been shown to exhibit neuroprotective properties. In the present study, we investigated the molecular mechanisms by which TNF receptor (TNFR)I mediates neuroprotection by comparing the gene expression profiles of lesioned cortex from WT and TNFRI KO mice after permanent middle cerebral artery occlusion. Several known neuroprotective molecules were identified as TNFRI targets, notably members of the Bcl-2 family, DNA repair machinery and cell cycle, developmental, and differentiation factors, neurotransmitters and growth factors, as well as their receptors, including EPO receptor (EPOR), VEGF, colony-stimulating factor receptor 1, insulin-like growth factor (IGF), and nerve growth factor (NGF). Further analysis showed that induction of EPOR and VEGF expression in primary cortical neurons after glucose deprivation (GD) largely depended on TNFRI and was further up-regulated by TNF. Also, EPO- and VEGF-induced neuroprotection against GD, oxygen-glucose deprivation, and NMDA excitotoxicity depended significantly on TNFRI presence. Finally, EPO prevented neuronal damage induced by kainic acid in WT but not TNFRI KO mice. Our results identify cross-talk between tissue protective cytokines, specifically that TNFRI is necessary for constitutive and GD-induced expression of EPOR and VEGF and for EPO-mediated neuroprotection.     

Idiopathic phalangeal acroosteolysis: a case report

Acroosteolysis is characterized by bone resorption in the fingers and toes and can occur in several diseases. Phalangeal acroosteolysis is a rare idiopathic form. We report a case in a 13-year-old girl with a 2-year history of swelling and skin ulcers of the second and third left fingers and second right finger. The fingers were abnormally short and the nails were hypertrophic. Roentgenograms disclosed terminal phalangeal resorption in the fingers and toes. Findings were normal from tests for inflammation and dysimmunity. Biopsies of the skin lesions showed fibrosis without inflammation. Neurological evaluation and electromyographic study were normal. Serological tests for syphilis were negative. Calcium and phosphate levels in blood and urine were normal. A diagnosis of idiopathic phalangeal acroosteolysis (Joseph and Shinz disease) was given. This inherited form of acroosteolysis is transmitted on an autosomal dominant or recessive basis. It affects the tips of the distal phalanges of the fingers and toes but occasionally spreads to other bones.     

High fibroblast growth factor 19 (FGF19) expression predicts worse prognosis in invasive ductal carcinoma of breast

Metabolic diseases like diabetes and obesity are major risk factors for breast cancer. Aberrant expression of metabolic effectors such as fibroblast growth factor 19 (FGF19) could be therefore associated with the disease. The expression of FGF19 was examined in 193 archival breast tumor samples by immunohistochemistry and evaluated semi-quantitatively by determining the staining index and correlating it with clinicopathological parameters using Fisher's exact test. The correlation between FGF19 expression and 5-year disease-specific survival rate was determined using the univariate Kaplan–Meier analysis. The prognostic value of FGF19 expression was evaluated using the multivariate Cox regression analysis. Of the 193 tumors analyzed, 40 % were classified with low FGF19 expression, whereas 60 % were categorized as tumors with high FGF19 expression. There was a highly significant correlation between high FGF19 expression and patients' age (p?=?0.008) as well as 5-year disease-specific survival (p?=?0.001). However, FGF19 expression did not show any significant correlations with other clinicopathological parameters, including hormonal status, tumor grade, tumor size, or lymph node status. Univariate Kaplan–Meier log rank analysis showed that patients with high FGF19 expression exhibited a significantly shorter disease-specific 5-year survival (p?=?0.007). This effect was exacerbated by lymph node metastasis (p?=?0.001), negative estrogen receptor (ER) status (p?=?0.002), or old age (p?=?0.013). Multivariate analysis showed that high FGF19 expression could be an independent prognostic marker of disease-specific survival in breast cancer patients (p?=?0.030). Quantification of FGF19 expression appears to provide valuable prognostic information in breast cancer, particularly in older patients with lymph node metastasis and negative ER status.     

Inspection of pharmacies in Morocco during the French protectorate 1912-1956

In Morocco, the inspection of the pharmacy as currently practiced has enjoyed a great evolution: from a small body born during the protectorate, which originally had two inspectors, it has become a well-organized and prioritized sector. This article revisits the birth and history of this inspection during the French protectorate. Based on the available literature, we examined and analyzed the arrangements related to the establishment of the inspection, its various reorganizations as well as the powers allocated to inspectors.     

Variceal Band Ligation in the Prevention of Variceal Bleeding: A Multicenter Trial

Background/Aim:

Variceal bleeding is a life-threatening complication of portal hypertension with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory. The study has been aimed at investigating the effectiveness of endoscopic band ligation in preventing upper gastrointestinal bleeding in patients with portal hypertension and to establish the clinical outcome of patients.

Patients and Methods:

We analyzed in a multicenter trial, the efficacy and side effects of endoscopic band ligation for the primary and secondary prophylaxis of esophageal variceal bleeding. We assigned 603 patients with portal hypertension who were hospitalized to receive treatment with endoscopic ligation. Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The primary end point was recurrent bleeding.

Results:

The median follow-up period was 32 months. A total of 126 patients had recurrent bleeding. All episodes were related to portal hypertension and 79 to recurrent variceal bleeding. There were major complications in 51 patients (30 had bleeding esophageal ulcers). Seventy-eight patients died, 26 deaths were related to variceal bleeding and 1 to bleeding esophageal ulcers.

Conclusions:

A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.