Assessment of prestin level changes as an inner-ear biomarker in patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: To assess the correlation of serum prestin level and audiological findings in adults with idiopathic sudden sensorineural hearing loss. METHODS: Audiometry and serum prestin measurements were performed at study entry (T0), at day 14 (end of treatment, T1) and at day 30 (T2). RESULTS: A total of 25 idiopathic sudden sensorineural hearing loss patients and 25 healthy adults were included. The geometric mean prestin level in the case and control groups at T0 was 227.7 pg/ml and 130.5 pg/ml, respectively. The geometric mean prestin level in the case group demonstrated a downward trend at T1 and T2 (214.0 pg/ml and 180.1 pg/ml, respectively; p < 0.001). Of 17 patients with high baseline prestin levels (over 150 pg/ml), prestin levels tended to decrease in 11 patients, and 5 of them (45.5 per cent) showed good recovery. CONCLUSION: The prestin concentrations increased in two-thirds of patients with idiopathic sudden sensorineural hearing loss. Future work is recommended to determine the location of injury.

Reciprocal assessment of urinary beta-2-microglobulin and BUN levels in renal dysfunction of neonates with birth asphyxia.

OBJECTIVE: Asphyxia at birth is one of the major causes of morbidity and mortality in all neonates due to various organ dysfunctions, for example, kidneys. Recent advances in this area have suggested new urinary proteins for the assessment of renal damage, including beta-2 microglobulin (ß2-MG). The aim of this study was to investigate the changes of urinary ß2-MG in asphyxiated neonates and to evaluate the value of combined detection of multiple biomarkers in the early diagnosis of acute kidney injury (AKI) in asphyxiated neonates. STUDY DESIGN: This case-control study was performed on 84 term neonates in two control and case groups who were hospitalized at the neonatal intensive care unit. Using the Sarnat scoring system, the asphyxiated neonates were neurologically divided. Renal function tests and urinary ß2-MG (uß2-MG) levels of participants who registered based on inclusion criteria were measured. The data analyzed using descriptive and inferential statistical tests. The diagnostic value of the biomarker was determined using receiver operating characteristic (ROC) curves. RESULTS: This study showed that uß2-MG was not a statistically significant difference in both asphyxiated neonates with AKI and non-AKI (p = .085). Whereas, uß2-MG levels were statistically significant in neurological grading of asphyxiated infants to two groups (p = .013). A new predictor, uß2-MG and blood urea nitrogen (BUN); named BB1, was substituted as the diagnostic value in neonates with asphyxia with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.88 (0.76-1.0). This AUC was significantly greater than the value for uß2-MG associated with AKI (p = .003). CONCLUSION: Our findings showed that mutual detection of uß2-MG levels with BUN should be an early indicator for the diagnosis of renal injury with greater specificity and improved prognostic accuracy after neonatal asphyxia.

Osteomyelitis and lung abscess due to Aspergillus fumigatus in a chronic granulomatous disease patient.

BACKGROUND AND PURPOSE: Chronic granulomatous disease (CGD) is an inherited disorder of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This disorder results in recurrent life-threatening bacterial and fungal infections. Aspergillus species are the most common fungal infections in these patients. CASE REPORT: Herein, we present a case of fungal infection in a girl with CGD. We confirmed aspergillosis through the positive microscopic and macroscopic examinations, as well as radiology results. Invasive aspergillosis in this patient with pneumonia, lung abscess, and osteomyelitis of the ribs was not initially treated with amphotericin B (Am B) and recombinant interferon-gamma. CONCLUSION: Among infectious diseases, fungal infections, in particular aspergillosis, remain a serious problem in CGD patients. Considering poor clinical response and deficient immune system, rapid diagnosis of fungal infection and optimizing the treatment of these patients are recommended.

Design of a new line in treatment of experimental rheumatoid arthritis by artesunate.

This study was aimed to evaluate the therapeutic potency of a new antimalarial drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally administration of artesunate (ARS) and methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was intermittent. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ARS and MTX were assessed using fibrosarcoma cell line. Our results showed that i.p. injection of artesunate to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cells infiltrate in joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following ARS therapy. Moreover, our radiographic results paralleled histological findings. Cytotoxicity analysis of ARS showed greater tolerability compared with MTX. Treatment with ARS significantly diminished nitric oxide formation in treated rats compared with untreated controls. Our findings revealed the therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate). This result may recommend it as a second-line drug in the treatment of rheumatoid arthritis.

Two matrix metalloproteinases inhibitors from Ferula persica var. persica.

Matrix metalloproteinases (MMPs) play a role in several physiologic and pathologic events. There is some evidence indicating the involvement of MMPs in tumor invasion and inflammatory diseases. Here we studied the chloroform extract of Ferula persica var. persica. The influence of these extracts vs. a reference drug, diclofenac sodium, on MMP production by the fibrosarcoma cell line was investigated using an in vitro cytotoxicity assay, sodium dodecyl sulfate-polyacrylamide, and gelatin zymography. The total extract of the roots was found to exhibit a selective inhibitory effect on tumor cell invasion. The bioactivity-guided fractionation of this extract led to the isolation of two compounds. These compounds showed highest MMP inhibitory effect at minimal toxic dose levels. Using conventional spectroscopy methods, the active fractions were identified as t-butyl 3-[(1-methylthiopropyl)dithio]-2-propenyl malonate (persicasulphide B) and umbelliprenin, previously isolated from F. persica var. latisecta. Since inhibition of MMP activity has been employed in modality therapy in diseases such as cancer, this compound might be promising in the preparation of anti-MMP therapeutic derivatives.

Treatment of experimental arthritis with M2000, a novel designed non-steroidal anti-inflammatory drug.

The current study was planned to explore the therapeutic potency of M2000 (beta-D-mannuronic acid), a novel designed non-steroidal anti-inflammatory drug (NSAID) in adjuvant-induced arthritis model. Arthritis was induced in Lewis rats by a single intradermal injection (0.1 ml) of heat-killed Mycobacterium tuberculosis (0.3 mg) in Freund's incomplete adjuvant into the right footpad. Fourteen days after injection of adjuvant, the contralateral left footpad volume was measured. The animals with paw volumes 0.37 ml greater than normal paws were then randomized into treatment groups. Orally and intraperitoneally administrations of test drugs (M2000, 40/mg/kg/day and indomethacin, 2/mg/kg/day) were started on day 15 post-adjuvant injection and continued until final assessment on day 25. The left hind limb was removed for histological evaluation. The WEHI-164 cell line was used for assaying tolerability and matrix metalloproteinase type 2 (MMP-2) activity. MMP-2 activity was assessed using zymography. Pharmacotoxicology study was carried out on animal models based on the evaluation of serum and urine determinants, histology of kidney, gastrointestinal tolerability and body temperature. Results showed that the orally administration as well as intraperitoneally injection of M2000 to arthritic rats induced a significant reduction in paw oedema. Histopathological assessment showed a reduced inflammatory cells infiltrate in joints of treated rats, as well as the number of osteoclasts present in the subchondral bone, tissue oedema and bone erosion in the paws were markedly reduced following M2000 therapy. Cytotoxicity analysis of M2000 showed a much higher tolerability compared with other tested drugs (diclofenac, piroxicam and dexamethasone). The inhibitory effect of M2000 in MMP-2 activity was significantly greater than that of dexamethasone and of piroxicam at a concentration of 200 microg/ml. Moreover, the toxicological study revealed that M2000 had no influence on serum (blood urea nitrogen, creatinine, triglyceride and cholesterol) and urine (urea and urinary protein excretion) determinants, glomerular histology and body temperature in normothermic rats and had no ulcerogenic effects on rats' stomach. Our data show that M2000, as a novel NSAID, could be strongly suggested as the safest anti-inflammatory drug for long-term administration.

Sodium alginate as a novel therapeutic option in experimental colitis.

The potential therapeutic effect of low-viscosity sodium alginate (LVA) was studied in a rat model of acute colitis induced by intracolonic administration of acetic acid. This experimental model produced a significant ulcerative colitis. Induction of colitis also significantly enhanced the serum and colonic mucosal cytokine (IL-6 and TNF-alpha) and eicosanoid (LTB4 and PGE2) levels, which paralleled with the severity of colitis. LVA solution was administered orally as drinking water at concentration of 0.5% (W/V) for 1 week. The tolerability and inhibitory effect of LVA on matrix metalloproteinase-2 (MMP-2) were tested using WEHI-164 cell line and zymography method. The results showed that LVA therapy is able to significantly reduce colonic damage score, histological lesion, serum and colonic mucosal IL-6, TNF-alpha, LTB4 and PGE2 levels in treated group compared with nontreated controls. Moreover, in vitro examinations revealed that treatment with LVA could diminish MMP-2 activity. It is concluded that LVA is able to suppress acetic acid-induced colitis in rats. Some of the action of LVA may be associated with its inhibitory effects on cytokine and eicosanoid production and MMP-2 activity. Our data suggest that LVA could potentially be a novel therapeutic option for inflammatory bowel disease.

Effect of piroxicam on matrix metalloproteinase 2 and apoptosis.

We examined the effect of a nonsteroidal anti-inflammatory drug (NSAID), piroxicam, on apoptosis and matrix metalloproteinase 2 (MMP-2) activity compared with diclofenac and dexamethasone. The fibrosarcoma (WEHI-164) cell line was used to assess tolerability, MMP-2 activity and apoptosis. Piroxicam, dexamethasone and diclofenac were used at concentrations of 10-200 microg/ml in triplicate and 2-fold dilutions. MMP-2 activity was assessed using zymography. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used. The results of this study show that piroxicam is able to diminish MMP-2 activity and induce apoptosis under in vitro conditions. Piroxicam also showed high tolerability compared with diclofenac and dexamethasone. In conclusion, piroxicam is able to induce apoptosis and suppress MMP-2 activity.

Tolerability and anti-inflammatory effects of glucuronoxylomannan in collagen-induced arthritis.

This investigation was planned to assess the therapeutic efficacy of glucuronoxylomannan (GXM) in collagen-induced arthritis (CIA). GXM was isolated from culture filtrate of Cryptococcus neoformans var. gattii, serotype C. CIA was induced by the immunization of Dark Agouti rats with bovine type II collagen in incomplete Freund's adjuvant. GXM solution at two doses, 25 and 50 mg/kg, was administered intraperitoneally. Onset of i.p. injections of GXM to prevention and treatment groups was days 0 and 10 postimmunization, respectively. The WEHI-164 cell line was used for assaying tolerability, matrix metalloproteinase type 2 (MMP-2) activity and apoptosis. MMP-2 activity was assessed using zymography. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling method was used. The results of this experiment showed that the treatment of CIA with GXM at a dose of 50 mg/kg could suppress disease development both prophylactically and therapeutically. This beneficial effect of GXM was associated with a significant decrease in the anti-CII antibody response compared with untreated rats. Moreover, GXM therapy could diminish MMP-2 activity, but it had no notable effect on apoptosis. GXM also showed a high tolerability compared with certain steroidal and non-steroidal anti-inflammatory drugs. We conclude that GXM suppresses the development of disease in CIA and it could be recommended as a new immunosuppressive and anti-inflammatory agent for further investigations.

Alteration in Matrix Metalloproteinases (MMPS) Activity in Fibroblast Cell Line by Dexamethasone: A Possible Mechanism in Corticosteroid-Induced Glaucoma.

Corticosteroids are often used as anti-inflammatory agents in a variety of inflammatory diseases. It is well established that long-term administration of corticosteroids predisposed the patients to develop glaucoma. Although the exact pathophysiology of steroid-induced glaucoma is unknown, it is assumed that Matrix metalloproteinases (MMPs) have a role in its pathogenesis. To study and estimate the pathophysiological effects of MMPs in glaucoma, we established an in vitro cell culture model. We also employed a precise proliferation assay to analyze cytotoxic effect of dexamethasone. The influence of dexamethasone on MMPs production was investigated using an in vitro gelatin Zymography. Cytotoxcity analysis of Dexamethasone revealed no significant cell death in low concentration. However, it caused 50% and 70% cell death at 80 and 100 mg/mL respectively. It also revealed an inhibitory effect on MMPs by dexamethasone in a dose dependent fashion. It may be concluded that an alteration in the level of MMPs expression by dexamethasone interferes with ocular fluid drainage and may contribute to the pathogenesis of glaucoma.