Both sunitinib and sorafenib are effective treatments for pheochromocytoma in a xenograft model

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors which develop from chromaffin cells of the adrenal medulla and extra-adrenal sites, leading to excess catecholamine release and hypertension. Many of the tumors are characterized by a high vascularity, suggesting the possible implementation of anti-angiogenic therapies for patients. Here, the efficacy of the tyrosine kinase inhibitors sunitinib and sorafenib was investigated in vivo and in vitro. Oral treatment with either sunitinib or sorafenib (40 mg/kg/day) for 14 days induced a marked reduction in the volume and weight of PC12 pheochromocytoma cell tumor xenografts in mice. Assessment of tumoral neo-angiogenesis, assessed by morphometric analysis of the vascular network after CD31 immunolabeling, showed that both sunitinib and sorafenib reduced the microvessel area (−85% and −80%, respectively) and length (−80% and −78%, respectively) in treated compared to control tumors. In addition, the number of vessel nodes was significantly lower in treated tumors (−95% and −84%, respectively). Furthermore, cleaved caspase 3 immunolabeling revealed a marked increase in the number of apoptotic cells in tumors from treated animals. Sunitinib and sorafenib could exert a direct effect on PC12 cell viability in vitro. While sunitinib induced a rapid (4 h) and pronounced (5-fold) increase in caspase-3/7-dependent apoptosis, sorafenib seems to exert its cytotoxic activity through a different mechanism. Altogether, our data demonstrate that sunitinib and sorafenib have the ability to impair pheochromocytoma development by inhibiting angiogenesis and reducing tumor cell viability. These results strongly suggest that both sunitinib and sorafenib could represent valuable therapeutic tools for pheochromocytoma.     

Cervical cancer in Tunisia: an epidemiological, clinical and pathological study

BACKGROUND: This study was undertaken to determine epidemiological and pathological profile of cervical cancer in Tunisia. DESIGN STUDY: Registration and analysis of all cervical cancer newly diagnosed during the year 1994 (year of general census) based on review of all pathology laboratory files in the country with exclusion of previously diagnosed cases according to clinical data. RESULTS: During the year 1994, 216 new cases were registered among which 195 cases (89.81%) were invasive carcinoma. The standardized incidence (invasive cancer) is 5.91 per 100000 women per year. The average age was 53.7 year. Sixty-three percent cases are diagnosed at an advanced stage (IIB, III, IV FIGO stages). Invasive carcinoma has distributed as follows: 177 cases (91.23%) were squamous invasive carcinoma, 17 cases (8.77%) were invasive adenocarcinoma. In the same year, 21 cases of in situ squamous carcinoma were registered with an average age equal to 44.21 year. Only one case of cervical cancer was a sarcoma (0.52%). CONCLUSION: The incidence of cervical cancer in Tunisia is relatively low in spite of the absence of a screening program. This may be related to monogamy and observance of legal age of marriage. Squamous invasive carcinoma is the most frequent pathological type. CONDENSATION: The incidence of cervical cancer in Tunisia is relatively low in spite of the absence of a screening program.     

Familial spastic paraplegia as the presenting manifestation in patients with purine nucleoside phosphorylase deficiency

We report two siblings with purine nucleoside phosphorylase deficiency revealed by isolated spastic paraplegia, whereas symptoms of immune deficiency did not become apparent until 3 years of age. As the concurrence of immunodeficiency and neurologic problems strongly suggests the diagnosis of purine nucleoside phosphorylase deficiency, special attention should be paid to counts of lymphocytes in any infant with spastic paraplegia.     

Left coronaroventricular microfistula

Left coronaroventricular microfistulae is a rare malformation. The authors report 11 cases of microfistulae between coronary arteries and left ventricle diagnosed by coronary arteriographies. These cases include 6 men and 5 women. Patient's mean age was 54.4 years. The symptoms were suggestive of coronary pathology. The ECG showed myocardial ischemia signs in 5 cases. The other patients had a positive exercise-test. Microfistulae originated from the left anterior descending artery were seen in 5 cases, from the right coronary artery in 2 cases, from the circumflex in 1 case and from the lateral artery in 1 case. The microfistulae originated from both left anterior descending artery and right coronary artery were observed in 2 patients. The main mechanism of myocardial ischemia seems to be related to the coronary steal phenomenon. The diagnosis of the microfistulae is based on coronary arteriography with late recorder angiographic images. The treatment is essentially medical. Surgical and transcatheter treatments are exceptional and must be considered in only severe forms with refractory medical treatment.     

Numerical–Experimental Analysis toward the Strain Rate Sensitivity of 3D-Printed Nylon Reinforced by Short Carbon Fiber

Despite the application of the Additive Manufacturing process and the ability of parts’ construction directly from a 3D model, particular attention should be taken into account to improve their mechanical characteristics. In this paper, we present the effect of individual process variables and the strain-rate sensitivity of Onyx (Nylon mixed with chopped carbon fiber) manufactured by Fused Filament Fabrication (FFF), using both experimental and simulation manners. The main objective of this paper is to present the effect of the selected printing parameters (print speed and platform temperature) and the sensitivity of the 3D-printed specimen to the strain rate during tensile behavior. A strong variation of tensile behavior for each set of conditions has been observed during the quasi-static tensile test. The variation of 40 °C in the platform temperature results in a 10% and 11% increase in Young’s modulus and tensile strength, and 8% decrease in the failure strain, respectively. The variation of 20 mm·s⁻¹ in print speed results in a 14% increase in the tensile strength and 11% decrease in the failure strain. The individual effect of process variables is inevitable and affects the mechanical behavior of the 3D-printed composite, as observed from the SEM micrographs (ductile to brittle fracture). The best condition according to their tensile behavior was chosen to investigate the strain rate sensitivity of the printed specimens both experimentally and using Finite Element (FE) simulations. As observed, the strain rate clearly affects the failure mechanism and the predicted behavior using the FE simulation. Increase in the elongation speed from 1 mm·min⁻¹ to 100 mm·min⁻¹, results in a considerable increase in Young’s modulus. SEM micrographs demonstrated that although the mechanical behavior of the material varied by increasing the strain rate, the failure mechanism altered from ductile to brittle failure.     

A comparative study of intratracheal and aerosolization instillations of bleomycin inducing experimental lung fibrosis in rat

We aimed to investigate in the present work, using metabonomics approaches, the scalability of lung fibrosis-biomarkers, in bleomycin (BLM) model of pulmonary fibrosis in rats. Sixty male Wistar rats, weighing 250?±?10?g, were randomly divided into three groups: a negative control group receiving normal saline treatment (G₁), an intratracheal BLM instilled group (G₂), and an aerosol BLM instilled group (G₃). Rats were investigated at various times after BLM instillation. Metabolic changes observed in different biofluids have been integrated into the results of the histological examination (increase in inflammation, fibrosis score, and TGF-β immunostaining) which provide a novel pathway of biomarkers in pulmonary fibrosis. These two BLM-models showed an efficacy in the production of pulmonary fibrosis in rats, accompanied by an oxidative stress in lung tissue as assessed by the increase of lipid peroxidation and the depletion in the level of antioxidant enzymes such as superoxide dismutase and catalase. The aerosol model was more advantageous showing fibrotic foci occupying the majority of the lung in contrast to intratracheal instillation characterized by a non-homogeneous distribution of the fibroblastic foci.