The expanding spectrum of a disease. Beh?et's disease associated with amyloidosis

In this report, we present a series of 6 patients with Beh?et's disease (BD) associated with amyloidosis whose illnesses date back at least 4 years. In all the cases, nephrotic syndrome heralded the onset of amyloidosis, which was diagnosed by percutaneous kidney biopsies. After the diagnosis of amyloidosis, all subjects received colchicine, and steroids were discontinued. Three patients have benefited from treatment. It was suggested that amyloidosis may be an intrinsic feature of BD or that the suppurative lesions may play a role in the accumulation of amyloid in the tissues. The literature was reviewed and discussed.     

The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma

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Nasal administration of metoclopramide from different dosage forms: in vitro,ex vivo,and in vivo evaluation

Nasal drug delivery is an interesting route of administration for metoclopramide hydrochloride (MTC) in preventing different kind of emesis. Currently, the routes of administration of antiemetics are oral or intravenous, although patient compliance is often impaired by the difficulties associated with acute emesis or invasiveness of parenteral administration. In this perspective, nasal dosage forms (solution, gel, and lyophilized powder) of MTC were prepared by using a mucoadhesive polymer sodium carboxymethylcellulose (NaCMC). In vitro and ex vivo drug release studies were performed in a modified horizontal diffusion chamber with cellulose membrane and excised cattle nasal mucosa as diffusion barriers. The tolerance of nasal mucosa to the formulation and its components were investigated using light microscopy. In vivo studies were carried out for the optimized formulations in sheep and the pharmacokinetics parameters were compared with oral solution and IV dosage form. The release of MTC from solution and powder formulations was found to be higher than gel formulation (p?<?0.05). Histopathological examination did not detect any severe damage. Hydroxypropyl-β-cyclodextrin (HPβCD) used in powder formulations was found to be effective for enhancing the release and absorption of MTC. In contrast to in vitro and ex vivo experiments nasal bioavailability of gel is higher than those of solution and powder (p?<?0.05). In conclusion, the NaCMC gel formulation of MTC with mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.     

Protection from cyclophosphamide-induced ovarian damage with bone marrow-derived mesenchymal stem cells during puberty

Objective: In female cancer survivors, the accelerated loss of primordial follicles may lead to premature ovarian failure. We investigated the protective effects of bone marrow derived mesenchymal stem cells (BMMSC) and gonadotropin releasing hormone analogue (GnRHa) against chemotherapeutic-induced ovarian toxicity in a rat model.

Material and methods: Forty-eight Wistar albino female rats were divided into four groups. Group 1 was composed of rats that were given 200?mg/kg cyclophosphamide injection for each cycle (two cycles for each rat). Both cyclophosphamide and 0.4?µg GnRHa were administered to Group 2. Cyclophosphamide and 4 million/kg BMMSC were administered to Group 3. Cyclophosphamide, GnRHa, and BMMSC were administered to Group 4. Germ cell apoptosis, DNA fragmentation and primordial follicular count were investigated with Cleave Caspase-9 and TUNEL analysis. The presence of the SRY gene on the Y chromosome in the ovary of the recipient female rats was checked with PCR.

Results: Immunohistochemical staining (IHS) of Caspase-9 and TUNEL was higher in Group 1 than in Group 3 (p?p?SRY gene was detected in Groups 3 and 4 with the PCR analysis. The mean primordal follicle count was lowest in Group 1 and the mean primordial follicle counts were higher in Groups 2 and 3 than in Group 1. The difference between Group 1 and Group 4 was not significant.

Conclusion: BMMSC therapy was found to be protective from germ cell apoptosis and DNA damage when it was used with chemotherapy regimens including alkylating agents.     

Comparison of hyaluronate/carboxymethylcellulose membrane and melatonin for prevention of adhesion formation in a rat model

BACKGROUND: To investigate the effectiveness of melatonin in preventing post-operative adhesion formation and to compare it with the efficacy of hyaluronate/carboxymethylcellulose membrane in a rat model. MATERIALS and METHODS: Following pilot studies, 35 rats were operated on in the full study. In 15 animals (group one), 10 standard lesions were inflicted in each uterine horn (total 30 horns) and melatonin was applied before closure of the abdomen. In the second group, 20 animals were operated on and one of the uterine horns (total 20 horns) with standard lesions was treated with hyaluronate/carboxymethylcellulose membrane and the other uterine horn served as a control. Second-look operations were performed 1 week later and adhesion scores were compared. RESULTS: The adhesion scores of uterine horns treated with melatonin and of uterine horns treated with hyaluronate/carboxymethylcellulose membrane were significantly lower than the scores of the controls (P < 0.001). There was no statistically significant difference between the adhesion scores of uterine horns treated with melatonin and of uterine horns treated with hyaluronate/carboxymethylcellulose membrane (P > 0.05). CONCLUSIONS: Both melatonin and hyaluronate/carboxymethylcellulose membrane were effective in prevention of adhesion formation in a rat uterine horn model.     

Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats

The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.     

Protective effects of chronic melatonin treatment against renal ischemia/reperfusion injury in streptozotocin-induced diabetic rats.

AIMS: The purpose of this study was to investigate the effects of chronic administration of melatonin on renal ischemia/reperfusion (IR) injury in streptozotocin (STZ)-induced diabetic rats. METHODOLOGY: Male Sprague-Dawley rats were divided into six groups: control (C), diabetes mellitus (DM), control+IR (C+IR), DM+IR, Melatonin+IR (Mel+IR), DM+Mel+IR. Diabetic and non-diabetic rats were given melatonin 4 mg/kg/day, i.p., for 15 days. The left renal artery and vein of rats were occluded for 30 min at the 18th day, followed by 24 h of reperfusion. RESULTS: In comparison with control group, the levels of malondialdehyde (MDA), protein carbonyl (PC) and and nitric oxide (NO) were determined to be higher in the renal homogenates of DM, DM+IR and C+IR groups. MDA and NO levels were found to be similar in the DM+melatonin+IR and control groups. The most significant histological damage was found in the DM+IR group and this damage was significantly reduced by melatonin. CONCLUSION: Chronic melatonin treatment reduces renal injury by reducing lipid oxidation and NO production in STZ-induced diabetic rats exposed to IR.     

Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats

To date, there have not been enough studies about the effects of curcumin against oxidative stress on sciatic nerves caused by streptozotocin (STZ) in diabetic rats. Therefore, this study was undertaken to determine whether curcumin, by virtue of its antioxidant properties, could affect the oxidant/antioxidant balance in the sciatic nerve and brain tissues of streptozotocin (STZ)-induced diabetic rats. A total of 28 rats were randomly divided into four groups of seven rats each: normal controls, only curcumin treated, diabetic controls, and diabetics treated with curcumin. Biomarkers-malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and NO levels-for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. We found a significant increase in MDA, NO, TOS, and OSI, along with a reduction in TAS levels in the brains and sciatic nerves of the STZ-induced diabetic rats (for both parameters p < 0.05). The MDA, TOS, OSI, and NO levels in these tissues were significantly reduced in the curcumin-treated diabetic group compared to the untreated diabetic group. In conclusion, the results of this study suggested that curcumin exhibits neuroprotective effects against oxidative damage in the brain and sciatic tissues of diabetic rats.     

Low-dose oral anticoagulation and antiplatelet therapy with St. Jude Medical heart valve prosthesis

BACKGROUND AND AIM OF THE STUDY: Since 1986, the St. Jude Medical (SJM) mechanical heart valve prosthesis has been implanted in patients at the authors' institution. We present our experience of low-dose oral anticoagulation and antiplatelet therapy following SJM valve implantation. METHODS: Among 2,585 patients (mean age 40.3 +/- 13.5 years) living in a rural environment, 865 underwent aortic valve replacement (AVR), 1,231 mitral valve replacement (MVR) and 489 double valve replacement (DVR). All patients received 2.5 mg/day warfarin and a combination of antiaggregation therapy (dypridamole 3 x 75 mg/day plus aspirin 100 mg/day), irrespective of their prothrombin time and cardiac rhythm. RESULTS: Postoperatively, 139 adverse events occurred (51 in AVR patients, 58 in MVR, 30 in DVR). Operative mortality rate was 5.9%, 4.7% and 6.1%, respectively, in the three groups (overall mortality rate 5.4%). The most frequent cause of operative mortality was low cardiac output. During follow up, there were 88 anticoagulant hemorrhages (1.2%/patient-year (pt-yr)), 11 paravalvular leaks (0.2%/pt-yr), 52 thromboembolisms (0.7%/pt-yr), 60 mechanical valve thromboses (0.8%/pt-yr) and 78 reoperations (1.1%/pt-yr). These complications occurred in 101 patients after AVR, in 125 after MVR, and in 63 after DVR (4.2%, 3.7% and 4.6% per pt-yr, respectively). Patient age (p = 0.0004), concomitant surgery (p = 0.0017) and late valve-related complications (p = 0.0159) were statistically significant mortality factors after AVR. Previous surgery was a significant risk factor for operative mortality after MVR (p <0.05). Female gender (p = 0.0059) and age (p = 0.017) were significant risk factors for operative mortality after DVR (p <0.01). CONCLUSIONS: Following implantation of the St. Jude Medical mechanical heart valve prosthesis, a fixed dose of 2.5 mg/day warfarin and combined dipyridamole/aspirin provided satisfactory results in terms of thrombosis, embolism and bleeding.