Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin‐induced mouse model of asthma

Background and objective: In asthma, reduced histone deacetylase activity and enhanced histone acetyltransferase activity in the lungs have been reported. However, the precise function of Sirtuin 1 (Sirt1), a class III histone deacetylase, and the effect of the Sirt1 activator SRT1720 on allergic inflammation have not been fully elucidated. Methods: The effect of SRT1720, a synthetic activator of Sirt1, in an ovalbumin (OVA)‐induced asthma mouse model was investigated. The effect of SRT1720 and resveratrol on OVA stimulation in splenocytes from OVA‐sensitized and challenged mice was also examined. Results: In OVA‐sensitized and challenged mice (OVA mice) compared with saline‐sensitized and challenged mice (control mice), Sirt1 messenger RNA expression in the lungs was decreased (P = 0.02), while cellular infiltration, airway eosinophilia and bronchoalveolar lavage (BAL) fluid levels of interleukin (IL)‐4, IL‐5 and IL‐13 were increased (P < 0.01). In OVA mice, SRT1720 treatment decreased total and eosinophil cell counts and IL‐5 and IL‐13 levels in the BAL fluid compared with the vehicle treatment (P < 0.05). In OVA mice, SRT1720 treatment also decreased inflammatory cell lung infiltrates histologically (P = 0.002). Both SRT1720 and resveratrol suppressed OVA‐induced cell proliferation and IL‐6 (P < 0.05) and tumour necrosis factor‐α (TNF‐α) (P < 0.05) production in splenocytes (P < 0.01). Conclusions: The Sirt1 activator SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA‐induced mouse model of asthma. SRT1720 and resveratrol suppressed OVA‐induced splenocyte proliferation and TNF‐α and IL‐6 production. Sirt1 activators might have beneficial effects in asthmatics by suppressing inflammation.     

Rheumatoid meningitis: an autopsy report and review of the literature

We report the clinical and autopsy findings of a 71-year-old Japanese woman with rheumatoid meningitis. This patient developed subacute meningitis during an inactive stage of rheumatoid arthritis (RA), and despite intensive examinations no causative agents or underlying disease could be identified except for RA. Based on persistent hypocomplementaemia and increased serum levels of immune complexes she was suspected of having vasculitis, and was treated with intravenous methylprednisolone (1000 mg/day for 3 days) followed by oral prednisolone. Soon after beginning treatment with corticosteroid her symptoms improved, in parallel with a decrease in cell counts and interleukin-6 in the cerebrospinal fluid. During tapering of oral prednisolone she died of a subarachnoid haemorrhage which was ascribed to a relapse of the meningitis. Autopsy demonstrated infiltration of mononuclear cells, including plasma cells, in the leptomeninges, mainly around small vessels, leading to a definite diagnosis of rheumatoid meningitis. When RA patients manifest intractable meningitis with a subacute course, this disease is important as a possible diagnosis even if the arthritis is inactive, and intensive treatment, including corticosteroid and immunosuppressants, should be positively considered as a therapeutic option as soon as possible because of the poor prognosis.Abbreviations RA Rheumatoid arthritis - IL Interleukin - DMARD Disease-modifying antirheumatic drugs - RF Rheumatoid factor - RAHA Rheumatoid arthritis haemagglutination - CSF Cerebrospinal fluid - TNF Tumour necrosis factor - MRI Magnetic resonance imaging     

Fluconazole in the treatment of tinea versicolor

Patients with tinea versicolor (TV, n = 603) aged 18–65 years entered into an open, randomized, multicenter study to investigate the efficacy and toleration of three dosage regimens of fluconazole. The study was conducted in 10 different centers in six cities in Egypt.
The patients were randomly assigned to one of three groups:
Group I: received single 150 mg fluconazole capsule repeated weekly for 4 weeks;
Group II: received two 150 mg capsules of fluconazole in a single dose repeated weekly for 4 weeks;
Group III: received two 150 mg capsules of fluconazole in a single dose that could be repeated 2 weeks later.
Five visits were scheduled for each group and the last follow-up visit was always 28 days after the last fluconazole dose. Response to treatment was assessed clinically and by microscopic examination of KOH mounts of skin scrapings, weekly and 28 days after the last fluconazole dose. The number of fluconazole doses administered was guided by clinical and mycologic response, and the dose was repeated only if the patient showed residual clinical lesions or positive microscopy for skin scrapings.
Final evaluation was rated as cure (disappearance of lesions with no or slight color changes), improvement (no scales while color changes were much less but still obvious), and failure (no or slight changes from baseline). Mycologic assessment was rated as eradication, persistence or relapse. All adverse events were recorded during the treatment period.     

Clarithromycin versus doxycycline in the treatment of rosacea

Forty patients with rosacea were entered into a study comparing clarithromycin with doxycycline in the systemic treatment of mild and severe rosacea. The patients, 25 women and 15 men, aged from 26 to 62 years, were subdivided into two homogeneous groups with regard to age, sex, and disease seventy. The first group of 23 patients, 14 women and 9 men, was treated with 250 mg of clarithromycin for 4 weeks twice daily, and then with 250 mg once daily for the following 4 weeks. The second group of 17 patients, 11 women and 6 men was treated with 100 mg of doxycycline for 4 weeks twice daily, and then with 100 mg once a day for the following 4 weeks. Both objective and subjective evaluations of the dermatosis were performed prior to therapy and after 4, 6, and 8 weeks of treatment.     

Trial of aripiprazole in the treatment of first-episode schizophrenia

Aims:  Aripiprazole is an atypical antipsychotic indicated for the treatment of adult patients with schizophrenia. It is effective and well tolerated in patients with schizophrenia or schizoaffective disorder. The aim of the present study was to investigate therapeutic efficacy and tolerability of aripiprazole in patients with first-episode schizophrenia.
Methods:  Twenty-one patients meeting the DSM-IV criteria for schizophrenia were recruited. The Positive and Negative Symptom Scale (PANSS) and the Clinical Global Impressions Scale (CGI) were completed at the beginning of the study and again after 1, 2, 4, and 8 weeks of aripiprazole treatment. Side-effects were analyzed using the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale. Weight was checked at each testing session, and prolactin levels were measured at baseline and after 8 weeks of aripiprazole treatment.
Results:  Significant benefits were observed after the first week of treatment. After 1 week of aripiprazole treatment, subscale and total scores on the PANSS had decreased significantly. This significant decrease was maintained throughout the study period. The mean score of CGI severity was also significantly different after 2 weeks of aripiprazole administration when compared to baseline score, and the significance was maintained thereafter. Weight did not significantly change after aripiprazole administration. Although mean prolactin level was decreased at 8 weeks, the difference was not significant.
Conclusions:  Aripiprazole is an effective and well-tolerated antipsychotic agent in patients with first-episode schizophrenia. Further investigations with larger samples are needed.     

Preoccupation with death as predictor of psychological distress in patients with haematologic malignancies

VOLLMER T.C., WITTMANN M., SCHWEIGER C. & HIDDEMANN W. (2011) European Journal of Cancer Care 20 , 403–411
Preoccupation with death as predictor of psychological distress in patients with haematologic malignancies The purpose of the present study was to identify preoccupation with death in relation to levels of psychological distress in patients with haematologic malignancies. One hundred and two inpatients with haematologic malignancies, treated with curative intent, and thirty‐three control inpatients with benign dysfunction participated in the present study. Psychological distress was measured with the Hospital Anxiety and Depression Scale and the Freiburg Questionnaire of Coping with Illness. Preoccupation with death was assessed with the Subjective Estimation of Sickness and Death Scale. Patients with haematologic malignancies had significantly more preoccupation with death than the control group. In patients with haematologic malignancies preoccupation with death was related to depressive coping style as well as symptoms of depression and anxiety; regression analyses reveal that the diagnosis of haematologic malignancy leads to stronger subjective feelings of being close to death, which in turn leads to more psychological distress. To the best of our knowledge this is the first study that quantitatively shows the existence of preoccupation with death in patients with haematologic malignancies and its association with psychological distress. Our findings indicate that patients who are treated with a curative regime need psychological intervention focusing on death‐related fear in order to prevent severe emotional distress.