Modulation of p53 transcriptional activity by PRIMA-1 and Pifithrin-alpha on staurosporine-induced apoptosis of wild-type and mutated p53 epithelial cells.

We recently argued for a major role of p53 in staurosporine(ST)-induced apoptosis of immortalized epithelial cells, depending on their p53 status. Here, we studied the effects of PRIMA-1 (p53 reactivation and induction of massive apoptosis) and Pifithrin-alpha (p fifty-three inhibitor) in combination with ST to reinforce our previous results by respectively restoring or inhibiting the p53 transcriptional activity in different cell lines.PRIMA-1 does modify neither expression of apoptosis-related proteins nor the percentage of wild-type p53 HeLa and CaSki cells with [symbol: see text]delta psi m and DNA cleavage, whilst it increases by 45% Bax expression and apoptosis of mutated p53 C33A cells. Pifithrin-alpha, does modify neither Bax expression nor apoptosis level of C33A cells, but readily inhibits both [symbol: see text]delta psi m and DNA fragmentation of p53wt cells with decreasing Bax expression. These data support the evidence that PRIMA-1 could be a good candidate, as an anti-cancer drug targeting mutant p53, in order to increase ST efficiency. Moreover, Pifithrin-alpha could be used in combination with ST and PRIMA-1 to prevent side effects of anti-tumor therapies in cells expressing mutant P53.

Mitochondrial translocation of p53 and mitochondrial membrane potential (Delta Psi m) dissipation are early events in staurosporine-induced apoptosis of wild type and mutated p53 epithelial cells.

The mitochondrial localization of p53 is an important event in p53-dependent apoptosis. Some p53 mutants defective for transcription also facilitate apoptosis through changes of the mitochondria. Here, apoptosis of HeLa and CaSki cells (p53(wt)), C33A and HaCat cells (p53(mt)) and SaOs-2 cells (p53 deficient) was induced by 300 nM staurosporine. We showed that wild-type p53, as well as p53 mutants, were transiently located to the mitochondria with changes in the mitochondrial membrane potential (Delta Psi m). However, in C33A cells harboring a p53 mutated on its DNA binding domain, Delta Psi m collapse and Sub-G1 DNA content were reduced compared to p53(wt) cells, whereas no significant difference was observed in HaCat cells with a p53 mutated on UV hot spots. In addition, inhibition of the mitochondrial permeability transition pores by cyclosporine A significantly reduced the Delta Psi m loss and the sub-G1 DNA content in p53 positive cells. These results indicate that Delta Psi m collapse is an early and necessary event, which plays an important role in apoptosis of immortal mammalian cells.

Intra-articular injections of hylan G-F 20 in patients with symptomatic hip osteoarthritis: an open-label, multicentre, pilot study.

OBJECTIVE: To obtain prospective data on feasibility and safety of intra-articular injections of hylan G-F20 in patients with symptomatic hip osteoarthritis (OA). METHODS: Fifty-seven patients with primary hip OA, Kellgren-Lawrence grade II-III, aged > or = 40 and walking pain 50-90 mm on a visual analogue scale (VAS) were enrolled in an open-label, multicentre pilot trial. Hylan G-F20 (2 ml) was injected intra-articularly (IA) in the hip under fluoroscopy at D0, and follow-up visits were performed at D7-30-60-90. The possibility of a second injection at D30-60 or 90 was considered if the reported pain level was equivalent to baseline. Adverse events, walking pain (VAS), WOMAC index, patient and physician's global assessment were recorded at each visit. RESULTS: Twenty-five patients 1 injection and 32 received 2 injections. Transient hip pain was reported following 10.1% of injections, but no patient withdrew from the study because of this. Two mild synovial fluid aseptic effusions occurred after the first injection. No systemic device-related adverse event was reported. Walking pain decreased from 69.3 mm at entry to 39.5 mm at the end point (p < 0.0001). All other outcome measures decreased significantly. CONCLUSION: Viscosupplementation with hylan G-F20 is feasible, easy to perform and well-tolerated in hip OA. A double-blind, controlled study should be performed to confirm data on its efficacy.

[Hyperkeratosis papilloma of the eyelid. An anatomic clinical case]. / Papillome hyperkératosique de la paupière. A propos d'une observation anatomo-clinique.

A clinicopathologic case of an 80-year-old male patient with a single cutaneous tumor on the upper part of the left eyelid is reported. It was a grayish and pigmented mass covered with a thick keratin layer, well circumscribed, and exophytic. After surgical removal, histopathology showed that the tumor had a papillomatous pattern and was growing under a thick layer of hyperkeratosis. It was a typical squamous cell papilloma. This tumor belongs to the benign eyelid tumor group and can be found on the eyelids of elderly people.

[Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo]. / Le chondroïtine sulfate dans le traitement de la gonarthrose et de la coxarthrose. Résultats à 5 mois, d'une étude prospective multicentrique, contrôlée, en double aveugle, versus placebo.

One hundred twenty patients with osteoarthritis of the knees and hips were entered into a randomized, placebo-controlled, double-blind trial designed to evaluate the effectiveness of chondroitin sulfate (Structum). The three-month treatment phase was followed by a two-month treatment-free phase to allow evaluation of carry-over effects. The main endpoint was use of nonsteroidal antiinflammatory drugs (expressed as mg of diclofenac equivalent). At completion of the three-month treatment phase, patients taking chondroitin sulfate (4 capsules/day) were using significantly less NSAIDs; this decrease persisted throughout the two-month treatment-free follow-up phase. The other parameters studied including visual analog scale assessment of pain, the Lequesne pain-function index, and overall patient and physician assessments, all showed a similar significant tendency. Tolerance was outstanding and no patients required premature withdrawal. These findings indicate that chondroitin sulfate is useful for the treatment of osteoarthritis, both as an agent slowly effective against symptoms and to reduce the need for NSAIDs. The carry-over effect of the drug suggests that intermittent administration may be appropriate.

A double blind, placebo controlled study of niflumic acid gel in the treatment of acute tendinitis.

Percutaneously administered niflumic acid gel (Niflugel R, Laboratories UPSA, Rueil Malmaison, France) was compared to placebo in a double blind, placebo controlled, multicentre study in the treatment of acute upper and lower limb tendinitis. Fifty nine subjects were enrolled in three centres and were randomly allocated to receive treatment with 2.5% percutaneous niflumic acid gel or placebo gel applied three times daily for 7 days. Clinical evaluations were carried out on inclusion and after seven days of treatment. The variables measured were pain felt by the patient and the investigators' and patients' overall evaluation of the treatments' efficacy. The patients also kept a daily record of pain scores. Any adverse events that occurred were noted. The results showed that niflumic acid gel was significantly better than placebo in improving patient signs as regards overall efficacy ratings. Global evaluation of efficacy rated by the investigator showed that 25/29 patients (86.2%) were healed or improved in the niflumic acid gel group compared with 11/27 patients (40.7%) on placebo, p = < 0.01. The overall assessment of tolerance showed no difference between groups. Only two minor adverse effects were reported in patients treated with niflumic acid gel, and they did not require patients to stop treatment. The study findings indicate that treatment with topical niflumic acid gel is effective in the treatment of tendinitis and results in improved clinical signs at the end of 7 days.

Clinical evaluation of niflumic acid gel in the treatment of uncomplicated ankle sprains.

A double-blind, placebo-controlled, multi-centre study was carried out to assess the efficacy and tolerability of percutaneous niflumic acid gel in the treatment of uncomplicated ankle sprains. Sixty patients were enrolled in three centres and were randomly allocated to receive treatment with 2.5% percutaneous niflumic acid gel or placebo gel applied 3-times daily for 7 days. Clinical evaluations were made on entry to the study, after 3 days and at the end of treatment. The major efficacy criteria were the pain felt by the patient and the investigators' and patients' global evaluation of effectiveness of the treatment. Adverse events that occurred were also noted. The results showed that topically applied 2.5% niflumic acid gel was superior to placebo in the treatment of ankle sprains in respect of all major parameters studied. Niflumic acid gel and the placebo were shown to be equally well tolerated. The study findings indicate that treatment with topical niflumic acid gel is effective in treating uncomplicated ankle sprains and results in improved clinical signs on Day 4 and after 7 days.

[Eyelid localization of a Merkel cell tumor (trabecular carcinoma)]. / Localisation palpébrale de la tumeur á cellules de Merkel (carcinome trabéculaire).

The authors present four cases of Merkel cells tumor of the eyelid. These cases conform to the standard clinical and histological criteria specified in the dermatological literature. Immuno-histochemical studies have been performed (specific neuron enolase, cytokeratin KL 1). Il the last case an ultrastructural study has made evident the characteristic neurosecretory granulations and intermediate filaments. Various hypothesis concerning the origin of this tumor are discussed in light of anatomical evidence.

[Ganglioneuroblastoma of the orbit]. / Ganglioneuroblastome de l'orbite.

Ganglioneuroblastoma a transitional tumor of sympathetic origin has not yet been described as involving orbit. It is characterized by a mixture of cells ranging from primitive neuroblast to well differentiated ganglion cells within a neurofibromatous tissue. The prognosis is uncertain, as the tumor may either undergo maturation into a ganglioneuroma or may metastasize widely and rapidly as in neuroblastoma. We may postulate a relationship between ganglioneuroblastoma and Recklinghausen's neurofibromatosis in view of the development of the tumor in conjunction with the phacomatosis.

[Value of alveolar lavage and transbronchial biopsy in the diagnosis of isolated sarcoid uveitis]. / Intérêt du lavage alvéolaire et des biopsies transbronchiques dans le diagnostic des uvéites sarcoïdosiques isolées.

The diagnosis of sarcoidosis is established by biopsy of sarcoid tissues demonstrating non-caseating granuloma, but difficulties arise when extra pulmonary organs are involved separately. Positive histologic signs can however be found in the lung even when there are no radiologic features. Bronchoalveolar lavage and biopsies were performed in 19 patients presenting severe, strictly isolated uveitis (5 cases of anterior uveitis, 3 cases of posterior uveitis and 11 cases of panuveitis). Criteria of positivity were non-caseating granuloma and lymphocytosis. Positive signs were obtained in 6 cases (31,5%); 1 case of posterior uveitis and 5 of panuveitis. There was no case of false positive results but one false negative result. There was a lack of correlation between results of these investigations and angiotensin converting enzyme blood levels. These investigations are non-invasive in experienced hands.

A comparative study of benoxaprofen and ketoprofen in ankylosing spondylitis.

Benoxaprofen, 600 mg once daily, was compared with ketoprofen, 100 mg twice daily, in a double-blind parallel study of 23 patients with definite active ankylosing spondylitis. Results were assessed using the following measurements: day pain, night pain, and spinal stiffness. Spinal stiffness was determined by means of standard clinical tests. Patient's evaluation and physician's overall assessment at the end of therapy also were taken into account. Under these conditions, the therapeutic response for benoxaprofen was good/very good, 8; fair, 2; and no response, 2. For ketoprofen, the response as good/very good, 5; fair 3; and no response 3. This study shows that benoxaprofen provides very good therapeutic effectiveness in the treatment of ankylosing spondylitis. This is confirmed by the absence of any statistically significant difference between the results observed with benoxaprofen and with ketoprofen, a drug known to be of value in ankylosing spondylitis. The clinical and biologic tolerance of benoxaprofen in this study was quite satisfactory.