Comparison of the protective effects of curcumin and caffeic acid phenethyl ester against doxorubicin-induced testicular toxicity

Whether testicular toxicity is mediated by matrix metalloproteinases (MMPs) is an important question that has not been examined. This study investigated the suppressive effect of curcumin and caffeic acid phenethyl ester (CAPE) on oxidative stress, apoptosis, and whether MMPs mediate doxorubicin (DOX)-induced testicular injury. Male rats were randomly divided into eight groups (n = 8 per group). The groups were as follows: sham, dimethyl sulphoxide (100 µL), DOX (3 mg/kg), CAPE (2.68 mg/kg), curcumin (30 mg/kg), DOX+CAPE (3 mg/kg DOX and 2.68 mg/kg CAPE), DOX+curcumin (3 mg/kg DOX and 30 mg/kg curcumin) and DOX+CAPE+curcumin (3 mg/kg DOX, 2.68 mg/kg CAPE and 30 mg/kg curcumin). Injections were administered daily for 21 days. The oxidative stress, MMPs, proinflammatory cytokines and apoptotic markers in the DOX group were higher than the sham group (p < .05); these measures were lower in the groups treated with CAPE and curcumin together with DOX compared with the DOX group (p < .05). The results showed that MMPs mediated DOX-induced testicular injury, but CAPE and especially curcumin suppressed testis injury and cell apoptosis by suppressing DOX-induced increases in MMPs, oxidative stress and proinflammatory cytokines. However, curcumin exhibited more pronounced effects than CAPE in terms of all studied parameters.     

Topometric and Tomographic Evaluation of Subclinical Keratoconus

ABSTRACT

Purpose

To investigate the corneal topometric and tomographic findings that can be used in the diagnosis of subclinical keratoconus.     

Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34⁺ cell dose was 4.8?×?10⁶/kg (range, 1.7 to 22.9; n?=?43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.     

The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model

This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.     

Suture anchor tenodesis in repair of distal Achilles tendon injuries

Background

Distal Achilles tendon avulsions are in the form of either bony and nonbony avulsion of Achilles tendon from its calcaneal insertion.

Methods

Four patients with distal Achilles tendon avulsions or ruptures which were treated with tendon to bone repair using suture anchors are presented here. Operated leg was immobilized in above-knee cast for 4 weeks while the patient walked non-weight-bearing. Then, cast was changed to below knee, and full weight-bearing was allowed. Patients underwent gait analysis minimum at first postoperative year.

Results

Mean American Orthopedics Foot Ankle Society ankle/hindfoot score of patients at last visit was 88.75 (range 85–100), and Achilles tendon total rupture score was 77.75 (range 58–87). Mean passive dorsiflexion of injured ankles (14° ± 5°) was lower than uninjured ankles (23° ± 9°). All the kinematic parameters of gait analysis were comparable to the uninjured side. Maximum plantar flexion power of injured ankle was 1.40 W/kg, and this was significantly lower than the contralateral side value 2.38 W/kg; (P = 0.0143).

Conclusions

There were no visually altered gait or problems in daily life. Suture anchor tenodesis technique of distal Achilles tendon avulsions was successful in achieving durable osteotendinous repairs.     

Factors influencing mortality in spontaneous gastric tumour perforations

Spontaneous perforation of gastric cancer is a serious complication with a very high incidence of mortality. In order to evaluate the prognostic factors influencing mortality in patients with gastric tumour perforations and to clarify the optimal surgical treatment, the records of patients at one centre during a 5-year period were evaluated retrospectively. Between 1995 and 2000, 14 patients with perforated gastric cancer were operated on in the Emergency Surgical Unit of a Turkish Hospital. This figure represents 3% of all the patients with gastric cancer who were treated during the same period. The hospital mortality was 36% in patients with perforations. The duration of symptoms suggesting perforation and the presence of pre-operative shock were predictive factors of mortality. It was concluded that those patients with pre-operative shock and delayed diagnosis should be treated with extra caution to decrease mortality. Perforation and peritonitis must be treated initially and elective radical surgery delayed.