In Vitro Analysis of CsA-Induced Hepatotoxicity in HepG2 Cell Line: Oxidative Stress and α2 and β1 Integrin Subunits Expression

Background

Cyclosporine A (CsA)-induced hepatotoxicity could be due to a reduction in α2β1 integrin expression that may either be from the direct effect of CsA itself or from reactive oxygen species (ROS) overproduction.

Objectives

In this study we aimed to identify the cellular mechanisms underlying CsA-induced hepatic injury by investigating the activation patterns of the antioxidant enzymes, using HepG2 as an in vitro model.

Materials and Methods

HepG2 cells were cultured with different concentrations of CsA (0, 0.1, 1, 10 μg/ml) for 72 h. Effect of CsA on, 1) cellular integrity, 2) glutathione reductase (GR) and glutathione peroxidase (GPx) activity, 3) cellular levels of glutathione (GSH), 4) intracellular ROS, 5) ALT and AST activities, 6) urea production and 7) α2β1 integrin expression were assayed.

Results

CsA treatment demonstrated a dose dependent increase in intracellular levels of ROS, GPx activity and decrease in GSH levels (P<0.05). GR activity was mildly attenuated in 1 and 10 µg/ml concentrations of CsA. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) levels increased in CsA treated cells, while urea synthesis was significantly decreased following treatment with higher concentrations of CsA (P<0.05). Significant down-regulation of β1integrin expression was observed in 1 and 10 µg/ml CsA treated cells while α2 integrin mRNA was significantly down-regulated in all CsA treated cells.

Conclusions

The observed reduction of α2β1 integrin expression following CsA treatment could be proposed as a possible pathway of CsA-induced hepatotoxicity. Further studies are required to elucidate whether this attenuated expression is due to the direct effect of CsA or caused by overproduction of ROS.     

The Effect of Octreotide on Urine Output During Orthotopic Liver Transplantation and Early Postoperative Renal Function; A Randomized,Double-Blind,Placebo-Controlled Trial

Background

Maintenance of the adequate intraoperative renal perfusion is very important during Orthotopic Liver Transplantation (OLT) to prevent acute renal failure.

Objectives

For the first time, this study was designed to survey the effects of octreotide on urine output during anesthesia for OLT and early postoperative renal function.

Patients and Methods

In this randomized double-blind placebo controlled clinical trial, 79 of 89 patients who underwent OLT and fulfilled the study requirement were randomly allocated into two groups. In the octreotide group, the patients received octreotide infusion from the start of the operation. On the other hand, the control group patients received physiologic saline infusion instead of octreotide. The Mean Arterial Pressure (MAP), heart rate, urine output, norepinephrine usage, and dosage during the three stages of OLT, and baseline and postoperative creatinine were recorded and compared between the two groups.

Results

No significant differences were found between the two groups regarding the demographic characteristics and graft factors (P > 0.05). However, urine output and MAP during the three stages of OLT were significantly higher in the octreotide group compared to the control group (P < 0.05). Moreover, no significant difference was observed between the two groups regarding baseline as well as postoperative creatinine (P > 0.05).

Conclusions

The results demonstrated that octreotide infusion during anesthesia for OLT not only augmented the vasoconstriction effect of norepinephrine to increase MAP, but also maintained better renal perfusion and urine output during the operation.     

Assessment of the uvulo-glossopharyngeal dimensions in patients with β-thalassemia major

Objectives

Thalassemia patients present varying degrees of craniofacial characteristics, while the morphology of the upper airway is less studied. The purpose of this study was to compare the uvula-glossopharyngeal dimensions (UGDs) of patients with β-thalassemia major (BTM) with non-thalassemic subjects who had similarities in the maxillo-mandibular skeletal pattern.

Subjects and methods

The material for this cross-sectional retrospective study consisted of lateral cephalograms of 40 BTM patients (23 males, 17 females, aged 9.5?±?0.97 years). These were compared with lateral cephalograms of a control group of 40 non-thalassemic subjects (23 males, 17 females, aged 11.0?±?0.87 years). The control group was chosen so that they had similarities with the BTM patients in the following cephalometric variables: SNA (in degree), SNB (in degree), ANB (in degree), and anterior facial height (N-Me).

Results

The following UGDs in thalassemic subjects were significantly shorter in patients with BTM: tongue length (P?<?0.05), the distance between the hyoid bone and the mandibular plane (P?<?0.01), and the vertical distance between hyoid bone and the C3-RGN line (line connecting third vertebra and retrognathion) (P?<?0.05). The middle airway space in BTM patients was significantly wider (P?<?0.05), and a trend was observed for the wider inferior airway space (P?=?0.07).

Conclusions

Based on this study, some UGDs in BTM patients were significantly different, compared to non-thalassemic subjects who had a similar maxillo-mandibular skeletal pattern. These findings may have implications for the long-term treatment of BTM patients; however, since groups were not exactly age-matched, the observed differences between groups could be attributed to either BTM, age, or both. Additional studies with age-matched subjects are needed to investigate the relationship between BTM and UGDs.     

Brain penetration and intracerebral haemorrhage following Jackson-Pratt drain insertion

Acta Neurochirurgica - A case of brain penetration with resulting intracerebral haemorrhage following Jackson-Pratt drain insertion is reported. The advantages of drain placement are discussed. The...     

Primary Kaposi's sarcoma of the lymph node in children

A case of primary Kaposi's sarcoma of the lymph node (single node involvement) is reported on here. It occurred in a white, Italian boy 10 years of age. An extensive review of the literature showed that this was only the second childhood case of the disease among non-acquired immune deficiency syndrome (AIDS)-related people of the Western world.     

Inhibition of intraocular fibrin formation after infusion of low-molecular-weight heparin during combined phacoemulsification-trabeculectomy surgery

PURPOSE: To evaluate the effect of intraocular infusion of dalteparin, a low-molecular-weight heparin (LMWH) administered in the infusion fluid to prevent early postoperative fibrin formation in combined phacoemulsification-trabeculectomy surgery (phacotrabeculectomy). SETTING: Farabi Eye Hospital, Tehran, Iran. METHODS: Standard combined phacotrabeculectomy was performed prospectively in a masked fashion in 60 eyes; 35 eyes received 5 IU/mL LMWH in the infusate and 25 eyes served as controls. Masked postoperative examinations assessed visual acuity, intraocular pressure (IOP), anterior chamber cell and flare, and fibrin formation with slitlamp examinations 1, 3, 7, 30, and 90 days after surgery. RESULTS: The rate of intraocular fibrin/membrane formation was significantly lower in the LMWH group than in the control group at each follow-up (P<.001, Student t test) . The amount of IOP was lower in LMWH group at each follow up (P<.01, Student t test). Final visual acuity was better in LMWH group (P = .03, Student t test). The frequency of synechia formation was lower in the LMWH group on day 90 (P = .002, chi-square test). CONCLUSIONS: Infusion of dalteparin, a LMWH, may be an effective inhibitor of postoperative fibrin formation in phacotrabeculectomy surgery. It may reduce the frequency of synechia formation and improve visual acuity. It may not be associated with increased risk for intraoperative or postoperative complications at the tested dose. This drug may be a useful adjunct in combined surgery.     

Inhibition of the cyclooxygenase pathway attenuates morphine-induced conditioned place preference in mice

Prostanoids are shown to be important lipid mediators, not only in periphery but also in the brain, where they appear to modulate synaptic transmission. Recent studies have demonstrated that cyclooxygenase (COX) pathway might modulate the neurotransmission of gamma-aminobutyric acid and dopamine in the central nervous system. In this study, we have evaluated the effects of indomethacin (a non-selective COX inhibitor) and celecoxib (a selective COX-2 inhibitor) on the acquisition of morphine-induced conditioned place preference (CPP) in male Swiss mice. Our data shows that morphine (2.5-7.5 mg/kg) induces place preference conditioning in a dose-dependent manner. Celecoxib (0.01-5 mg/kg) and indomethacin (1 mg/kg) fail to produce a significant CPP or conditioned place aversion (CPA); however, higher doses of celecoxib (10 mg/kg) and indomethacin (5 mg/kg) induce CPA. Co-administration of celecoxib (0.5-5 mg/kg) or indomethacin (1-5 mg/kg) with morphine during the conditioning phase, blocked the acquisition of morphine CPP. These results indicate that the reward properties of morphine can be modulated by inhibiting COX activity in mice.     

Refractive outcome of silicone oil removal and intraocular lens implantation using laser interferometry

PURPOSE: To evaluate the refractive outcome of silicone oil removal and intraocular lens (IOL) implantation using laser interferometry. METHODS: Thirteen silicone oil-filled eyes of 12 patients were included in the study. IOL power calculation was performed using laser interferometry (IOLMaster V1.1; Carl Zeiss, Jena, Germany). All of these eyes underwent silicone oil removal and cataract extraction with IOL implantation. Post-operative refraction was evaluated. RESULTS: The mean deviation of the final post-operative refraction (spherical equivalent) was -0.30+/-0.91 D (range, -1.87 to +1.3) at 12 weeks. The mean axial length of the eyes was 22.99+/-0.84 mm (range, 22.07-25.24 mm). No major complications occurred intra- or post-operatively. CONCLUSION: Laser interferometry appears to be a feasible and satisfactorily accurate method to calculate IOL power in some silicone oil-filled eyes. Further studies comparing this technique to others are warranted.     

Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial

Depression is a serious disorder in today's society, with estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As a therapeutic plant, saffron is considered excellent for stomach ailments and as an antispasmodic, to help digestion and to increase appetite. It is also used for depression in Persian traditional medicine. Our objective was to assess the efficacy of the stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6-week double-blind, placebo-controlled and randomized trial.Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton rating scale for depression score of at least 18. In this double-blind, placebo-controlled, single-centre and randomized trial, patients were randomly assigned to receive a capsule of saffron 30 mg[sol ]day (BD) (Group 1) or a capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, Crocus sativus produced a significantly better outcome on the Hamilton depression rating scale than the placebo (d.f. = 1, F = 18.89, p < 0.001). There were no significant differences in the two groups in terms of the observed side effects.The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.