Thrombosis of the abdominal aorta in newborn: About two cases.

BACKGROUND: Aortic thrombosis in neonates is a rare phenomenon, and in most cases iatrogenic. An early recognition of the clinical features and an immediate intervention can offer a better prognosis, and thus preventing morbidity such as limb amputation, and even mortality. METHODS: We present two cases of full-term newborns with a thrombosis of the abdominal aorta hospitalized in the neonatal intensive care unit of Mohammed VI University Hospital in Marrakech in 2017 and 2019. RESULTS: The two patients presented swelling and cyanotic lower limbs. Doppler ultrasound revealed a pathological lower limb blood flow as a result of a thrombosis of the abdominal aorta. Both patients underwent an anticoagulant therapy, the first one benefited from a surgical thrombectomy, he developed a reperfusion syndrome with alveolar hemorrhage, and passed away as a result of a cardiorespiratory arrest. However the second patient got amputated of the right foot, his clinical evolution was favorable with a good healing of the surgical wound without recurrence of any thrombosis. CONCLUSION: Through those cases clinicians should be aware of the first clinical signs of this condition in order to offer a rapid and successful management.

Dizziness and renal failure revealing the Von Hippel Lindau disease.

The germinal mutation of the Von Hippel Lindeau (VHL) tumor suppressor gene predisposes to the development of benign or malignant richly vascularized tumors. VHL disease is an autosomal-dominant disorder with complete penetrance at the age of 60 years. Screening for people at risk is strongly recommended, and careful monitoring allows treatment of the tumor lesions as early as possible. A 42-year-old man sought medical consult for hematuria, disabling dizziness and balance disorders lasting for two months. The neurological examination revealed the presence of a kinetic cerebellar syndrome. The cerebro-spinal magnetic resonance imaging revealed multiple hemangioblastomas, both encephalic and medullar. Abdominal computed tomography revealed a big solid mass in the left kidney and multiple intra-parenchymal cystic lesions in the right kidney and the pancreas. The diagnosis of VHL disease was strongly suspected. The operative indication of brain damage and renal mass have been submitted. The pathological study of the renal surgical specimen revealed a clear cell carcinoma. The post-operative course was uneventful and all the symptoms have disappeared. Genetic study and close follow-up are recommended for this disease.

Effectiveness of internet-based cognitive behaviour therapy for panic disorder in routine psychiatric care.

OBJECTIVE: Guided Internet-based cognitive behaviour therapy (ICBT) for panic disorder has been shown to be efficacious in several randomized controlled trials. However, the effectiveness of the treatment when delivered within routine psychiatric care has not been studied. The aim of this study was to investigate the effectiveness of ICBT for panic disorder within the context of routine psychiatric care. METHOD: We conducted a cohort study investigating all patients (n = 570) who had received guided ICBT for panic disorder between 2007 and 2012 in a routine care setting at an out-patient psychiatric clinic providing Internet-based treatment. The primary outcome measure was the Panic Disorder Severity Scale-Self-report (PDSS-SR). RESULTS: Participants made large improvements from screening and pretreatment assessments to posttreatment (Cohen's d range on the PDSS-SR = 1.07-1.55). Improvements were sustained at 6-month follow-up. CONCLUSION: This study suggests that ICBT for panic disorder is as effective when delivered in a routine care context as in the previously published randomized controlled trials.

Possible pathogenic role of the transmembrane isoform of CD160 NK lymphocyte receptor in paroxysmal nocturnal hemoglobinuria.

PIGA mutations in paroxysmal nocturnal hemoglobinuria (PNH) patients lead to a glycosylphosphatidylinositol (GPI)-linked membrane proteins expression deficiency. Herein, we report the constitutive expression of the transmembrane CD160 (CD160-TM) activating receptor on non PIGA-mutated PNH patients circulating NK cells. In healthy individuals, only the GPI-anchored isoform of CD160 receptors is expressed on the circulating NK lymphocytes, while the transmembrane isoform appears after ex vivo activation. Similarly to CD160-GPI, we identified CD160-TM as a receptor for the MHC class I molecules. We demonstrate that PNH patients NK lymphocytes spontaneously produce significant amounts of IFN-γ that is inhibited by anti-CD160-TM or anti-MHC class I mAbs. These results indicate that circulating NK cells from PNH patients exhibit a self-MHC class I molecule reactive effector function, which could be mediated through the recruitment of CD160-TM receptor. Our data provide new insights regarding the possible role of CD160-TM on PNH patients NK lymphocytes and in the pathogenesis of the disease.

Characterization of the harmful effect of olive mill wastewater on spearmint.

In this study, changes in viability, biomass production, essential oil yield and essential oil composition of Mentha spicata L. (spearmint) exposed to olive mill wastewater (OMW) were investigated. Spearmint cuttings were sensitive to OMW and, after 6h of incubation in raw or diluted OMW, their viability was null. The short contact of raw OMW with mint cuttings caused an irreversible damage in rhizogenesis and shoots development. Roots were more sensitive to phytotoxicity than shoots. In a field essay, spearmint showed a good capability to recover when OMW was spread at 8 l m(-2) at the vegetative phase of growth (45 days after plantation). At this dose, a slight increase of mostly of the mint essential oil constituents was obtained. When the dose applied was 16 l m(-2), phytotoxicity was manifested by a high reduction of biomass and essential oil yield. The essential oil composition was also affected and a disappearance of many of mint essential oil constituents was observed with an increase of 59% for carvone, the major compound of spearmint essential oil. As far as we know, this is the first report on the effect of field application of OMW on an aromatic plant essential oil yield and composition.

[Orbital epidermoid cyst. Case report]. / Kyste épidermoïde intraorbitaire. A propos d'un cas.

Epidermoid tumors represent 1% of all primary intracranial tumors. Most of them occur intradurally in cerebellopontine angle and parasellar citerns. The intra-orbital location accounts for 4 to 5% of all primary intra-orbital tumors. We report the case of a 23-year-old girl with progressive right proptosis who had developed 6 months earlier. The tumor was removed via an external orbitotomy approach. Histology confirmed the diagnosis.

A role for tissue transglutaminase in alpha-gliadin peptide cytotoxicity.

In coeliac disease, gliadin peptides p56-88, p57-68 and p31-49 have been demonstrated to be involved in the pathogenic damage of the small intestine via their immunogenicity or toxicity to epithelial cells. To try to understand the mechanism of their toxicity, we investigated the effect of synthetic peptides (p31-49, p56-88, p57-68, p69-82) and of their deamidated analogues on Caco2 and FHs 74 Int cell toxicity and tissue tranglutaminase activity. Apoptosis, necrosis and cell viability were assessed by flow cytometry, and peptide deamidation was determined indirectly by measuring its capacity to inhibit tTG activity. The results showed that p56-88 and p57-68 reduced cell growth and concomitantly inhibited tTG activity in both cell types. This effect was abolished when Caco2 cells were treated with antibodies to tTG. Deamidated peptide p57-68 (E(65)) lost practically all of its inhibitory effect on cell growth and on tTG activity. Cellular toxicity was also observed with p31-49, which was not a substrate for tTG. p69-82 was not cytotoxic but became so when glutamine 72 was substituted by glutamic acid. These findings provide evidence for the existence of three types of toxicity among gliadin peptides: (i) peptides that are intrinsically toxic and are not substrates of tTG; (ii) peptides that are non-toxic but become so when they act as substrates of tTG; and (iii) peptides that are non-toxic and are not substrates of tTG but become so when deamidated. A mechanism other than that involving tTG could be responsible for the deamidation of glutamine residues of gliadin in the intestinal tract.

Development of an immunocapture method for measuring IgA antibodies to tissue transglutaminase in the sera of patients with coeliac disease.

One of the most reliable sero-diagnostic tests for coeliac disease (CD) is the measurement, by ELISA, of serum IgA antibodies to tissue transglutaminase (tTG) adsorbed to the wells of microtitre plates. In spite of its reliability, however, some discrepancies exist with the results obtained by the antiendomysium histological assay (EMA) and by biopsy the accepted gold standard. Among the reasons for these differences in titres between the ELISA and the last 2 mentioned assays are the conformational changes that proteins undergo on adsorption and the importance of conformational epitopes on tTG for diagnosing CD. To address this problem, a novel procedure was developed using guinea-pig tTG (gptTG) free in solution to interact with IgA antibodies in the sera of CD patients. Any immune complexes so formed are then captured by anti-tTG antibodies preadsorbed to the wells of microtitre plates. This immunocapture method was optimized for the amount of soluble gptTG needed to interact with all the IgA's anti-tTG present in fixed dilutions of serum samples, the amount of rabbit IgG anti-gptTG used to coat the wells of microtitre plates and the order of addition of the reaction components. Comparison of the IgA titres obtained by immunocapture with those by EMA and ELISA (adsorbed tTG) on 9 highly positive and 6 weakly positive sera from clinically characterized CD patients and 5 negative sera from non-CD control subjects revealed that the IgA titres by the immunocapture procedure were well correlated with those obtained by EMA, whereas the titres on ELISA showed discrepancies with both immunocapture and EMA.

[Hibernoma: a rare case of massive weight loss]. / L'hibernome: une cause rare d'amaigrissement massif.

Hibernoma is a rare soft tissue benign tumor composed of cells similar to those of brown fat observed in fetus and hibernating animals. Brown fat has thermogenous properties, by the way of carbohydrates and lipid catabolism, and can be of an important mean in thermoregulation. A massive weight loss is a rarely reported sign in patients with hibernoma. We report herein the case of a 47 man with a history of isolated weight loss, of 16 kg over 4 months. Clinical examination has shown a swelling of the right flank. Surgical resection has been made and histopathological examination has shown hibernoma. The post-operative weight gain confirmed the relationship between hibernoma and weight loss.

Successful treatment in two cases of steroid-dependent cutaneous polyarteritis nodosa with low-dose methotrexate.

To the best of our knowledge, only 3 cases of cutaneous polyarteritis nodosa (PAN) treated successfully with methotrexate (MTX) have been reported in the medical literature. We report 2 further cases of steroid-dependent cutaneous PAN treated successfully with low-dose weekly MTX therapy. The clinical and biological tolerance of MTX was excellent. The cutaneous lesions started to regress within 3 weeks. One of the patients reported full recovery which lasted 2 years after stopping the therapy. So, MTX seems to be an interesting therapy in the treatment of PAN because of its relatively low toxicity, its simple use, its quick action and prolonged results after MTX has been stopped.

Transglutaminase-mediated cross-linking is involved in the stabilization of extracellular matrix in human liver fibrosis.

BACKGROUND/AIMS: Lysyl oxidase-mediated cross-linking contributes to the stabilization of collagen in liver fibrosis. We have investigated transglutaminase-mediated cross-linking, to determine if it participates in the stabilization of extracellular matrix in human liver fibrosis. METHODS: Transglutaminase activity was assessed in vitro by incorporation of biotinylated amine into liver proteins. The product of the transglutaminase-catalyzed cross-linking reaction, Nepsilon(gamma-glutamyl)lysine, and the extracellular proteins cross-linked by it, were localized by immunohistochemistry in fibrotic livers. The cross-linked complexes were extracted from liver tissue, immunopurified and characterized by Western blot. RESULTS: Transglutaminase, detected by immunohistochemistry, Western blot and by enzymatic activity, was found in higher amounts in fibrotic than in normal liver. The Nepsilon(gamma-glutamyl)lysine cross-link, undetectable in normal liver, was present extracellularly in fibrotic liver, where it was co-distributed with osteonectin, mostly in inflammatory areas submitted to an intense remodeling. Cross-linking of osteonectin by transglutaminase was confirmed by Western blot. In parasitic fibrosis transglutaminase also originates from the parasite. CONCLUSIONS: Transglutaminase-mediated cross-linking occurs in liver extracellular matrix during the early, inflammatory, stage of liver fibrosis, whereas cross-linking by pyridinoline occurs mostly later in the fibrotic process. This could lead to the development of new anti-fibrotic treatments targeted to a specific stage of fibrosis.

In vivo regulation of glutamine synthetase activity in the marine chlorophyll b-containing cyanobacterium Prochlorococcus sp. strain PCC 9511 (oxyphotobacteria).

The physiological regulation of glutamine synthetase (GS; EC 6.3.1.2) in the axenic Prochlorococcus sp. strain PCC 9511 was studied. GS activity and antigen concentration were measured using the transferase and biosynthetic assays and the electroimmunoassay, respectively. GS activity decreased when cells were subjected to nitrogen starvation or cultured with oxidized nitrogen sources, which proved to be nonusable for Prochlorococcus growth. The GS activity in cultures subjected to long-term phosphorus starvation was lower than that in equivalent nitrogen-starved cultures. Azaserine, an inhibitor of glutamate synthase, provoked an increase in enzymatic activity, suggesting that glutamine is not involved in GS regulation. Darkness did not affect GS activity significantly, while the addition of diuron provoked GS inactivation. GS protein determination showed that azaserine induces an increase in the concentration of the enzyme. The unusual responses to darkness and nitrogen starvation could reflect adaptation mechanisms of Prochlorococcus for coping with a light- and nutrient-limited environment.

Regulation of glutamine synthetase by metal-catalyzed oxidative modification in the marine oxyphotobacterium Prochlorococcus.

The inactivation of glutamine synthetase (GS; EC 6.3.1.2) by metal-catalyzed oxidation (MCO) systems was studied in several Prochlorococcus strains, including the axenic PCC 9511. GS was inactivated in the presence of various oxidative systems, either enzymatic (as NAD(P)H+NAD(P)H-oxidase+Fe(3+)+O(2)) or non-enzymatic (as ascorbate+Fe(3+)+O(2)). This process required the presence of oxygen and a metal cation, and is prevented under anaerobic conditions. Catalase and peroxidase, but not superoxide dismutase, effectively protected the enzyme against inactivation, suggesting that hydrogen peroxide mediates this mechanism, although it is not directly responsible for the reaction. Addition of azide (an inhibitor of both catalase and peroxidase) to the MCO systems enhanced the inactivation. Different thiols induced the inactivation of the enzyme, even in the absence of added metals. However, this inactivation could not be reverted by addition of strong oxidants, as hydrogen peroxide or oxidized glutathione. After studying the effect of addition of the physiological substrates and products of GS on the inactivation mechanism, we could detect a protective effect in the case of inorganic phosphate and glutamine. Immunochemical determinations showed that the concentration of GS protein significantly decreased by effect of the MCO systems, indicating that inactivation precedes the degradation of the enzyme.

The cell cycle and induction of apoptosis in a hamster fibrosarcoma cell line treated with anti-cancer drugs: its importance to solid tumour chemotherapy.

The induction of apoptosis by anticancer drugs and its relationship to stages of the cell cycle was studied in cells derived from a solid tumour; a highly malignant hamster fibrosarcoma (Met B). Asynchronously proliferating cells were treated with a wide variety of agents such as actinomycin-D, 1-beta-D-arabinofuranosyl cytosine, camptothecin, cisplatin, cyclophosphamide, daunorubicin, 5-flurouracil, 6-mercaptopurine, hydroxyurea, ionomycin, methotrexate and vincristine. With the exception of cyclophosphamide and hydroxyurea, a 36 h exposure to these drugs resulted in inhibition of cell growth and apart from cyclophosphamide, hydroxyurea. 6-mercaptopurine and cisplatin the induction of apoptosis. Studies using a decreased concentration of drug and exposure time (12 h) followed by examination of cells using flow cytometry indicated that most drugs were capable of affecting cell cycle progression without induction of apoptosis. However when cells were synchronised at G0/G1, S and G2/M phases and then exposed to these decreased concentrations of drug apart from 6MP an HU, apoptosis was observed and for the majority of drugs it took place in the same phase in which progression through the cell cycle was blocked by the drug. Cells synchronised in G0/G1 phase were more susceptible to methotrexate, whereas S-phase cells were more susceptible to camptothecin and 5-flurouracil and G2/M phase cells more susceptible to actinomycin D, 1-beta-D-arabinofuranosyl cytosine, daunorubicin and cisplatin. In contrast, vincristine blocked cells in G2/M phase but exerted its apoptotic effect in S-phase cells, ionomycin had no effect on the cell cycle, but G2/M cells appeared to be more susceptible to the effect of this drug. These data indicate that entry into apoptosis by this fibrosarcoma may occur at any point in the cell cycle. They also demonstrate a correlation between the action of some anticancer drugs on the cell cycle and the subsequent induction of apoptosis which may be useful in chemotherapeutic design.

Forceful epidural injections for the treatment of lumbosciatic pain with post-operative lumbar spinal fibrosis.

OBJECTIVE: To evaluate the efficacy of forceful epidural corticosteroid injections in lumbosciatic pain ascribed to post-operative lumbar spinal fibrosis. METHOD: Randomized controlled study comparing forceful injections via the sacral hiatus of 125 mg prednisolone acetate + 40 ml saline (treatment group) and injections via the same route of 125 mg prednisolone acetate alone (control group). Results were compared after six and 18 months. The main evaluation criterion was a subjective assessment of overall efficacy done by the patient using a seven-level scale. RESULTS: After six months, the proportion of patients who were relieved of their sciatica was significantly higher in the forceful injection group (n = 29; 45%) than in the control group (n = 31; 19%) (p = 0.03). Success rates for low back pain were 29% and 6% in the forceful injection and control groups, respectively. Among secondary efficacy criteria, nerve root pain evaluated on a visual analog scale and by Schöber's index showed significantly greater improvement in the forceful injection group than in the control group. After 18 months, results were still in favor of the forceful injection group, with success rates of 39% for the sciatica and 31% for the low back pain. The proportion of patients who returned to work was similar in the two groups. CONCLUSION: Although mediocre overall, the results of forceful epidural corticosteroid injections are better than those of simple epidural injections of a corticosteroid alone. Given the paucity of effective treatments for lumbosciatic pain apparently due to postoperative fibrosis, forceful injections should be given a place in the treatment of this condition.

The importance of the GTP-binding protein tissue transglutaminase in the regulation of cell cycle progression.

Tissue transglutaminase (tTgase) is a GTP-binding Ca(2+)-dependent enzyme which catalyses the post-translational modification of proteins via epsilon(gamma-glutamyl) lysine bridges. Recent evidence suggests that the GTP-binding activity of tTgase may be important in intracellular signaling thus explaining some of the diverse suggested roles for the enzyme. In the following work a malignant hamster fibrosarcoma (Met B) has been stably transfected with both the full length tTgase cDNA (wild type) and a mutant form of the cDNA whereby the active site cysteine (Cys 277) has been replaced by serine. Expression of this mutant cDNA leads to a protein with GTP binding activity which is deficient of protein crosslinking activity. When synchronised into S-phase and allowed to progress through the cell cycle tTgase transfected clones (both mutant and wild type), when compared to transfected controls, show a delayed progression from S-phase to G2/M when analysed by flow cytometry which appears to be elicited by the G-protein activity of the tTgase.

Transfection of tissue transglutaminase into a highly malignant hamster fibrosarcoma leads to a reduced incidence of primary tumour growth.

Reduced expression of the tissue transglutaminase in both murine and human tumours has been consistently associated with tumour growth and progression. To investigate the functional effects of transglutaminase expression we have transfected a constitutive human tissue transglutaminase expression construct into a highly malignant hamster fibrosarcoma cell line Met B. Met B clones expressing the exogenous tissue transglutaminase exhibited a reduced incidence of primary tumour formation and an increased adherence to tissue culture plastic and fibronectin coated surfaces when compared to transfected and non transfected control cells. Transglutaminase transfected clones exhibited no significant differences in their growth rates measured in vitro, cell morphology or levels of spontaneous apoptosis measured by the determination of detergent insoluble apoptotic envelopes. The data demonstrates a suppressive effect of tissue transglutaminase on tumour growth and confirms its importance in the phenotypic changes associated with the cancer process.