Ciblage des récepteurs de la somatostatine dans les tumeurs neuroendocrines gastroentéropancréatiques (TNE-GEP) : quels radiotraceurs pour quelles tumeurs ?

Topographic and functional imaging hold a key position in endocrine oncology. In vivo somatostatin receptor scintigraphy using Indium-111 labeled DTPA-octreotide, a tracer with preferential affinity for the somatostatin receptor subtype 2 (sst2), is the gold-standard for initial diagnosis of gastroenteropancreatic neuroendocrine tumours (GEPNETs). Due to the detection limits of scintigraphy, other metabolic imaging modalities are required. Positron emission topography (PET) offers whole body scanning, facilitates tumour localization, and assesses the metastasis statement of the tumour. ¹⁸F-FDG is the most frequent radiotracer used in clinical practice because of its availability, but its interest is demonstrated only in undifferentiated GEPNETs. More recently, ¹⁸F-DOPA PET showed a high sensitivity in particular in carcinoid tumours detection. PET using different ⁶⁸Ga-labeled-somatostatin analogs with high affinity for sst2 displayed better results than SRS in GEPNETs primary tumour and metastasis detection, especially when fusion with TDM images was performed. Using similar metabolic targets, peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-octreotate and ⁹⁰Y-DOTA-TOC, is indicated in disseminated GEPNETs forms with an efficiency of 30 % and a minor toxicity.     

Sequence optimization in a sequencing batch reactor for biological nutrient removal from domestic wastewater

The purpose of this work was to determine optimum sequence retention times for nutrient removal with low-cost using very short aeration time in an SBR treating domestic wastewater. During the study, four different CYCLEs were evaluated, with the highest removal efficiencies recorded for the CYCLE with fill, anaerobic, aerobic1, anoxic, aerobic2, settle, and decant sequences operated at retention times of 0.5, 2, 2, 1, 0.75, 1, and 0.5 h, respectively. For this CYCLE, the removal efficiencies of chemical oxygen demand (COD), total Kjeldahl nitrogen (TKN), ammonia nitrogen (NH₃–N), total phosphorus (TP), and ortho-phosphate (PO₄–P) were found, on average, to be 91, 78, 85, 87, and 83%, respectively. The optimum sequence retention time was determined via the analysis of variance (ANOVA) using the Matlab software (Mathworks Inc.). The data indicated that the total time of the aerobic sequences was shorter than those of previous studies for similar level of removal efficiencies in all parameters including N and P.     

Developmental and reproductive patterns of Triatoma brasiliensis infected with Trypanosoma cruzi under laboratory conditions

The aim of this work was to study the interaction between Trypanosoma cruzi-1 and Triatoma brasiliensis. A group of 1st instar nymphs was initially fed on T. cruzi-infected mice and a control group was fed on uninfected mice. From the second feeding onwards, both groups were otherwise fed on non-infected mice. The resulting adults were grouped in pairs: infected male/uninfected female, uninfected male/infected female, infected male and female and uninfected male/uninfected female. The infection affected only the 1st instar nymphs, which took significantly more time to reach the 2nd instar than uninfected nymphs. The differences in the molting time between the infected and uninfected nymphs from the 2nd to the 5th instars were not statistically significant. Both groups presented similar rates of nymphal mortality and reproductive performance was not significantly affected by infection in any of the treatments.     

Estimation of the potential fertility based upon non-return rates of bulls: using polyacrylamide gel instead of cervical mucus in the sperm penetration test

In the present study, we aimed to develop a polyacrylamide gel that could be used instead of bovine cervical mucus in the cervical mucus penetration test (CMPT) to obtain coherent and replicable results in bulls. The frozen semen samples of six Holstein bulls, which were divided into two fertility groups as low and high according to their non-return rate (NRR), were used. In this study, the modified CMPT (mCMPT) was carried out within 0.25 mL transparent plastic straws with an inner diameter 1.7 mm. The penetration ability of spermatozoa to bovine cervical mucus and to polyacrylamide gels swollen with two different solutions [NaCl (G1) and PBS (G2)] was compared. For the penetration test, the straws filled with cervical mucus and both gels were dipped into thawed semen samples and incubated at 37 degrees C for 15 min. After the incubation, straws were frozen in liquid nitrogen vapour and stored at -20 degrees C. On the evaluation day, the frozen straws were cut at 1.5-1.75 cm (penetration distance range=PDR1), 3.25-3.5 cm (PDR2) and 5.0-5.25 cm (PDR3), beginning from open-end of the straws. The separated frozen parts were then immediately transferred onto special counting slides by pushing with a mandrel and left to thaw. Thawed samples were covered with cover glass and penetrated spermatozoa in these parts were counted. The relation between the results and fertility of bulls was determined. In the tests performed using mucus, the number of spermatozoa determined in the high fertility group was found to be higher at PDR3 (p<0.0001) compared to the low fertility group, while in G1 spermatozoa number was significantly higher at PDR1 and PDR3 (p<0.0001). However, in G2 medium, no significant difference was observed between either of the fertility groups with respect to spermatozoa number determined at all distance ranges. In the study, we have determined that the gel swollen with NaCl produces better results and this gel can be used instead of bovine cervical mucus for the CMPT. Therefore, we have concluded that the penetration test performed by polyacrylamide gel swollen with NaCl can be a suitable technique for estimation of the potential fertility of bull spermatozoa.     

Differential diagnosis of Charcot arthropathy and osteomyelitis

Foot problems are common causes of morbidity in patients with diabetes mellitus. Foot ulcers are the leading cause of hospitalization in diabetic patients. Bones may be involved in two different clinical conditions: osteomyelitis and Charcot osteoarthropathy. Osteomyelitis usually develops by spreading from contiguous soft tissue to underlying bone. Charcot foot is deformation of foot as a result of muscle athrophy, bone and joint structure changes in a joint as a secondary complication of neuropathy. To distinguish bone infection from non-infectious bone disorders as in Charcot joint may be difficult, especially if there is no skin ulceration. So, the mere absence of skin ulcers does not exclude the diagnosis of osteomyelitis.     

Homozygous mutations in fibroblast growth factor 3 are associated with a new form of syndromic deafness characterized by inner ear agenesis, microtia, and microdontia

We identified nine individuals from three unrelated Turkish families with a unique autosomal recessive syndrome characterized by type I microtia, microdontia, and profound congenital deafness associated with a complete absence of inner ear structures (Michel aplasia). We later demonstrated three different homozygous mutations (p.S156P, p.R104X, and p.V206SfsX117) in the fibroblast growth factor 3 (FGF3) gene in affected members of these families, cosegregating with the autosomal recessive transmission as a completely penetrant phenotype. These findings demonstrate the involvement of FGF3 mutations in a human malformation syndrome for the first time and contribute to our understanding of the role this gene plays in embryonic development. Of particular interest is that the development of the inner ear is completely disturbed at a very early stage--or the otic vesicle is not induced at all--in all of the affected individuals who carried two mutant FGF3 alleles.     

A microscopic study of kidney tissue in Familial Mediterranean Fever patients

Familial Mediterranean Fever (FMF) is an autosomal recessive hereditary disease leading mostly to renal failure and nephrotic syndrome. The ultrastructure of kidney has not been fully investigated in FMF associated renal disease. The aim of this study is to provide further evidence on the ultrastructure of kidney in patients with FMF who suffer from renal disease. Renal biopsies obtained from two patients who were diagnosed with FMF renal disease complications were examined. Examination of renal tissue by light and electron microscopy identified degenerations both in tubules and the filtration barrier. Foot processes were partly effaced. Amorphous material was found in thickened glomerular basement membranes. Fibrous material deposits in thick Bowman's capsule wall were also seen. Finally, degeneration in the form of folding of plasma membrane and vacuolization as well as fusion in mitochondria cristae, was observed. Accumulation of tissue remnants in the lumen was also found in tubules.     

Thermodynamic benchmark study using Biacore technology

A total of 22 individuals participated in this benchmark study to characterize the thermodynamics of small-molecule inhibitor-enzyme interactions using Biacore instruments. Participants were provided with reagents (the enzyme carbonic anhydrase II, which was immobilized onto the sensor surface, and four sulfonamide-based inhibitors) and were instructed to collect response data from 6 to 36 degrees C. van't Hoff enthalpies and entropies were calculated from the temperature dependence of the binding constants. The equilibrium dissociation and thermodynamic constants determined from the Biacore analysis matched the values determined using isothermal titration calorimetry. These results demonstrate that immobilization of the enzyme onto the sensor surface did not alter the thermodynamics of these interactions. This benchmark study also provides insights into the opportunities and challenges in carrying out thermodynamic studies using optical biosensors.     

Mycothiol import by Mycobacterium smegmatis and function as a resource for metabolic precursors and energy production

Mycothiol ([MSH] AcCys-GlcN-Ins, where Ac is acetyl) is the major thiol produced by Mycobacterium smegmatis and other actinomycetes. Mutants deficient in MshA (strain 49) or MshC (transposon mutant Tn1) of MSH biosynthesis produce no MSH. However, when stationary phase cultures of these mutants were incubated in medium containing MSH, they actively transported it to generate cellular levels of MSH comparable to or greater than the normal content of the wild-type strain. When these MSH-loaded mutants were transferred to MSH-free preconditioned medium, the cellular MSH was catabolized to generate GlcN-Ins and AcCys. The latter was rapidly converted to Cys by a high deacetylase activity assayed in extracts. The Cys could be converted to pyruvate by a cysteine desulfhydrase or used to regenerate MSH in cells with active MshC. Using MSH labeled with [U-(14)C]cysteine or with [6-(3)H]GlcN, it was shown that these residues are catabolized to generate radiolabeled products that are ultimately lost from the cell, indicating extensive catabolism via the glycolytic and Krebs cycle pathways. These findings, coupled with the fact the myo-inositol can serve as a sole carbon source for growth of M. smegmatis, indicate that MSH functions not only as a protective cofactor but also as a reservoir of readily available biosynthetic precursors and energy-generating metabolites potentially important under stress conditions. The half-life of MSH was determined in stationary phase cells to be approximately 50 h in strains with active MshC and 16 +/- 3 h in the MshC-deficient mutant, suggesting that MSH biosynthesis may be a suitable target for drugs to treat dormant tuberculosis.