N-acetyl cysteine in prevention of amphotericin- induced electrolytes imbalances: a randomized,double-blinded,placebo-controlled,clinical trial

Purpose

The aim of this study was to evaluate the effectiveness of oral n-acetyl cysteine, as a potential nephroprotective agent, in preventing and/or attenuating amphotericin B-induced electrolytes imbalances.

Methods

During a one year period, patients were to receive conventional amphotericin b for any indication for at least one week and were randomly allocated to receive either placebo or 600 mg oral n-acetyl cysteine twice daily during the treatment course of amphotericin b. Demographic and clinical data of the study population were gathered. Different aspects of amphotericin b nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and potassium wasting were assessed. Each patient was monitored for any adverse reaction to n-acetyl cysteine. Sixteen and 14 patients in the n-acetyl cysteine and placebo groups completed the study, 3incidences of hypokalemia (75 % versus 70 %; P?=?0.724) and hypomagnesemia (30 % versus 20 %; P?=?0.468) did not differ significantly between placebo and NAC groups, respectively. Although the rate of AmB nephrotoxicity was higher in the placebo than in the NAC group (60 % versus 40 %), this difference was not statistically significant (P?=?0.209) even after adjusting for probable associated factors of amphotericin b nephrotoxicity (P?=?0.206). The incidence as well as time of onset of electrolyte abnormalities also did not differ significantly between placebo and n-acetyl cysteine groups. About 44 % of n-acetyl cysteine recipients experienced new onset nausea and a mild unpleasant taste during the study.

Conclusion

Oral n-acetyl cysteine during the amphotericin B treatment course was not significantly effective in preventing or mitigating different features of its nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting.     

The effects simultaneous inhibition of dipeptidyl peptidase-4 and P2X7 purinoceptors in an in vivo Parkinson’s disease model

Metabolic Brain Disease - Loss of dopaminergic neurons following Parkinson’s disease (PD) diminishes quality of life in patients. The present study was carried out to investigate the...     

Efficient Diagnosis and Treatment Follow-Up of Human Brucellosis by a Novel Quantitative TaqMan Real-Time PCR Assay: a Human Clinical Survey

Rapid and effective diagnosis of brucellosis is a challenge for clinicians. Even when diagnosis is on time and therapy is initiated, meticulous follow-up appointments are crucial for ensuring the efficacy of the treatment. Due to shortcomings of serological methods, molecular diagnosis, especially real-time PCR, is becoming a main approach in laboratory diagnostics. Thus, the development of efficient procedures and standardization of the PCR tests will have a great impact on the precise detection and quantification of bacterial DNA loads, which is valuable for the medical management of brucellosis patients. We developed a new TaqMan real-time PCR directed to bcsp31, a shared gene of the brucellae. The bcsp31 gene fragment was cloned into pJET1.2. Recombinant pJET1.2-bcsp31 was linearized by HindIII digestion, and the product was used for the preparation of a standard curve. A panel of Brucella spp. and non-Brucella pathogens was tested. No bacterial genomes other than those of the brucellae were detected. According to the results, specificity of the method was 100%. In a clinical assessment, the positive-control group comprised 37 patients with microbiologically confirmed brucellosis, and 25 healthy individuals served as the negative-control group. By the end of the treatment period, there was a significant decrease in the DNA load of the 37 brucellosis patients, which persisted for the 4 weeks of monitoring after treatment, suggesting that our proposed method is an efficient monitoring tool. Serum samples prior to any treatment were collected from the 25 serologically suspicious patients and assessed by our method; 72% of these patients tested positive for brucellosis.     

Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling

Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.     

Early results after minimal lobectomy for benign nodular goiter

Following traditional operations (enucleation and subtotal resection) for benign nodular goiters recurrences may develop. Reoperations for this condition can cause complications, such as hypoparathyroidism and damage of the recurrent laryngeal nerve. That is why total thyroidectomy is recommended by many specialists in benign thyroid disease. We performed lobectomy on one side, and, if necessary, partial resection on the other side. Lobectomy was performed on one side in 31 cases, with partial resections on the other side in 73 patients. We tried to identify the parathyroid glands and both recurrent laryngeal nerves. Postoperative complications were evaluated. Temporary dysfunction of the recurrent laryngeal nerve was detected in 2.3%, permanent damage in 1.1%. Temporary hypocalcaemia developed in 16.4%, permanent hypocalcemia in 1.9%. Two reoperations were necessary for bleeding. Because of the low postoperative complication rate we recommend this method as an alternative to thyroidectomy for benign nodular goiters. We know that our favourable results can be compared with traditional subtotal resection and thyroidectomy when long term results of thyroid function and data about nodular recurrences will be collected.