E-selectin ligand–1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-β

The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. As TGF-β signaling is a critical determinant of growth plate homeostasis, skeletal dysplasias are often associated with dysregulation of this pathway. The context-dependent action of TFG-β signaling is tightly controlled by numerous mechanisms at the extracellular level and downstream of ligand-receptor interactions. However, TGF-β is synthesized as an inactive precursor that is cleaved to become mature in the Golgi apparatus, and the regulation of this posttranslational intracellular processing and trafficking is much less defined. Here, we report that a cysteine-rich protein, E-selectin ligand–1 (ESL-1), acts as a negative regulator of TGF-β production by binding TGF-β precursors in the Golgi apparatus in a cell-autonomous fashion, inhibiting their maturation. Furthermore, ESL-1 inhibited the processing of proTGF-β by a furin-like protease, leading to reduced secretion of mature TGF-β by primary mouse chondrocytes and HEK293 cells. In vivo loss of Esl1 in mice led to increased TGF-β/SMAD signaling in the growth plate that was associated with reduced chondrocyte proliferation and delayed terminal differentiation. Gain-of-function and rescue studies of the Xenopus ESL-1 ortholog in the context of early embryogenesis showed that this regulation of TGF-β/Nodal signaling was evolutionarily conserved. This study identifies what we believe to be a novel intracellular mechanism for regulating TGF-β during skeletal development and homeostasis.     

A rare cause of deep peroneal nerve palsy due to compression of synovial cyst – Case report

INTRODUCTIONSynovial cyst is a rare cause of compression neuropathy and its differential diagnosis can be misleading.PRESENTATION OF CASEThis article presents clinical, radiological, and histological findings of deep peroneal nerve palsy due to compression of a synovial cyst in a 30-year-old patient admitted with sudden drop foot.DISCUSSIONFocal nerve entrapment in lower extremity due to synovial cystis a rare entity. Differential diagnosis is important. Surgical excision is the main treatment method with high success rate.CONCLUSIONSynovial cyst compression which can be treated easily with surgical excision should be considered in rapidly progressed drop foot.     

The impact of depression and ghrelin on body weight in migraineurs

Background

Comorbidity of migraine with anxiety and depression may play a role in the link between migraine and obesity. We examined the moderating and mediating roles of ghrelin in the relationship between depression (and anxiety) and body weight in newly diagnosed migraineurs.

Methods

Participants were 63 newly diagnosed migraine patients (using the ICHD-II criteria) and 42 healthy volunteers. Body mass index (BMI) was calculated by measuring height and weight. Ghrelin was assessed at fasting. Depression was assessed with the Hamilton Depression scale, and anxiety with the Hamilton Anxiety scale.

Results

The data did not support the mediating role of ghrelin in the relationship between depression (or anxiety) and BMI for either the migraine or the control group. The interaction between ghrelin and depression as well as anxiety was significant for the migraine group, but not for the control group. Depressed (or anxious) migraineurs had a positive association between ghrelin and BMI, whereas for the non-depressed (or non-anxious) migraineurs this association was negative.

Conclusions

Depression and anxiety moderated the effect of ghrelin on BMI for migraineurs. Management of anxiety and depression might be regarded as part of migraine treatment.     

The effect of growth hormone treatment on bone mineral density in prepubertal girls with Turner syndrome: a multicentre prospective clinical trial

Background Patients with Turner syndrome (TS) are treated with GH to increase adult height. Although it is well established that GH promotes longitudinal bone growth, the effects of GH treatment on bone density are less clear. Objective To determine how GH treatment affects trabecular bone mineral density (BMD) in girls with TS at prepubertal ages in a prospective multicentre study. Patients and method Twenty‐two patients with TS in the prepubertal period with a mean age of 9·8 ± 2·5 (range 3·6–12·8) years were included in the study. All girls with TS underwent measurement of areal BMD using dual‐energy X‐ray absorptiometry (DXA) to obtain pretreatment anteroposterior (AP) lumbar spine values at L1–L4. Patients received GH (Genotropin) subcutaneously for 1 year at a dose of 0·05 mg/kg/day. Height and weight were measured at 3‐monthly intervals. The AP lumbar spine areal BMD was remeasured using the same technique after 1 year of treatment. Lumbar spine BMD Z‐scores and volumetric BMD (vBMD) Z‐scores were calculated using national standards. Results The height SDS of our cases showed a significant increase with GH therapy. The pretreatment lumbar spine (L1–L4) BMD Z‐score was –1·2 ± 1·2 SD and the vBMD Z‐score was –0·8 ± 1·6 SD. There were no significant changes in these values after 1 year of GH treatment. Prepubertal TS girls more than 11 years of age had lower vBMD Z‐scores (–1·7 ± 1·7 SD) than the girls aged less than 11 (–0·1 ± 1·0 SD) (P < 0·05) at the onset of therapy. No significant changes were observed in these values after 1 year of GH therapy. Conclusions Osteopaenia becomes apparent in prepubertal TS patients as they reach pubertal age. BMD evaluation may be necessary in these prepubertal TS girls at diagnosis. Short‐term GH therapy in these TS patients does not have a significant effect on bone density when measured at a site with a predominance of trabecular bone.     

Bilateral Freiberg’s disease in adjacent metatarsals

Freiberg’s disease usually affects the second and, less commonly, the third metatarsal heads [Helal and Gibb in Foot Ankle 8(2):94–102, 1987]. It was mainly observed unilaterally in adolescent females (F/M: 3/1–4/1) (Hay and Smith in The Foot 2:176–178, 1992). Bilateral occurrence and adjacent metatarsal involvement has been previously reported separately [Maresca et al. in Arthroscopy 12(1):103–108, 1996; Rafee et al. in Foot Ankle Surg 12:153–155, 2006]. The cases presented here involve two female patients aged 42 and 72 with bilateral Freiberg’s disease in both the second and third metatarsal heads. To our knowledge, this is the first report of such involvement of both the second and third metatarsal heads.     

Spectral analysis of EEG in normal and sulfite oxidase deficient rats under sulfite administration

This article investigated the possible neurotoxic effect of sulfite in normal and sulfite oxidase (SOX) deficients rats by evaluating EEG spectral analysis. Rats were divided into four groups: control (C), sulfite treated (25 mg/kg) (ST), SOX deficient (SD), and sulfite treated SOX deficient (STSD) groups. The qEEG spectral analyses of two spectral parameters including power and relative power were performed. The mean power of SD group was found to be increased compared to the all other groups and returned to control levels after sulfite administration. The power of the four frequency bands (delta, theta, alpha, beta) of the SD group corresponds to the mean power. EEG relative power increased in the delta band with concomitant decreases in power measured in the alpha frequency range. It was concluded that exogenous administration of sulfite affected the brain electrical activity in SOX deficiency, and improved neuroprotection.     

MGMT immunoexpression in growth hormone-secreting pituitary adenomas and its correlation with Ki-67 labeling index and cytokeratin distribution pattern

Recent publications suggest the utility of temozolomide (TMZ) in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to TMZ is inversely correlated with tumoral expression of O-6 methylguanine DNA methyl transferase (MGMT). Therefore, we aimed to assess MGMT immunoexpression in pure GH-secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI and cytokeratin (CK) distribution pattern. Our material consisted of 36 GH-secreting pituitary adenomas (21 female,15 male, mean age 42.5±10.5), operated at our center between 2003 and 2010. Immunostaining for MGMT, Ki-67, and CK was performed using avidin-biotin-peroxidase complex method. Immunoreactivity for MGMT and Ki-67 was evaluated microscopically and recorded as percentages of positive nuclear immunostaining. CK distribution pattern was also evaluated microscopically and assoreted into dot-like and nondot-like pattern subtypes. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, and 4=>50%. Staining for MGMT was <10% (score 1) in 30 (83.3%), 10-25% (score 2) in 3 (8.3%), 25-50% (score 3) in 2 (5.6%) and >50% (score 4) in 1 (2.8%) of the tumors, respectively. There was no correlation between Ki-67 LI and CK distribution pattern with MGMT immunoreactivity (P>0.05). Data from the current study suggest a large proportion of GH-secreting adenomas, including those with dot-like CK distribution pattern and high Ki-67 LI, demonstrate negative/low MGMT immunoreactivity and could be treated with TMZ, if conventional treatment fails.     

Comparison of antioxidant capacities of Ganoderma lucidum (Curtis) P. Karst and Funalia trogii (Berk.) Bondartsev & Singer by using different in vitro methods

The aim of the study was to investigate antioxidant activities of Ganoderma lucidum and Funalia trogii. Ethanol and water crude extracts from G. lucidum and F. trogii were investigated for their antioxidant capacity in some different assays, namely, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, metal chelating activity against ferrous ions, and plasma lipid peroxidation inhibitory. In addition, the amounts of total phenol, ascorbic acid, β-carotene, and lycopene components in the extracts were determined. Among the four mushroom extracts, G. lucidum water extract and G. lucidum ethanol extract showed the highest scavenging activity against DPPH radicals (50% inhibitory concentration?=?0.055?±?0.001?mg/mL). Total phenol was the major antioxidant component found in the mushroom extracts. These results showed that G. lucidum may be used in pharmaceutical applications because of its effective antioxidant properties.     

The Effect of Donor- and Recipient-Related Factors on Corneal Graft Survival in Penetrating Keratoplasty

Purpose: To investigate the impact of donor and recipient factors on graft survival in penetrating keratoplasty (PK).

Material and Methods: This retrospective study included 365 eyes that underwent PK using corneas from 231 donors between June 2010 and June 2015. Patients were divided into three groups (group 1: primary endothelial diseases; group 2: iatrogenic endothelial disorders; and group 3: other pathologies with a healthy endothelium) according to PK indications. The primary outcome measure was corneal graft survival at the last visit (clear or opaque). Graft clarity was assessed using Kaplan–Meier survival analysis.

Results: The most frequent PK indication was keratoconus (KC) (20.5%) followed by pseudophakic bullous keratopathy (PBK) (18.9%). Donor age had a negative impact on endothelial cell density (ECD) measured by an eye bank specular microscope (p < 0.001). Median best-corrected visual acuity in logarithm of the minimum angle of resolution units increased from 2.1 to 0.8 at 1 year after PK (p < 0.001). The clear graft rate was 96.7% at year 1, 88.8% at year 2, and 85.5% at year 3. Overall graft survival was 84.9% during a median of 39 months (range: 24–79 months) of follow-up. A higher graft survival rate (67.2%) was observed in KC compared to PBK during 6 years (p < 0.001). Recipients younger than 50 years of age showed a better graft survival rate than those older than 70 years of age (p = 0.037). Donor ECD, time between excision and death, and preservation time had no significant effect on graft survival. Frequent graft rejection episodes (GREs) and additional procedures during surgery had a negative impact on graft survival (p < 0.001 and p = 0.014, respectively). A worse graft survival was observed in group 2 compared to groups 1 and 3 (p = 0.042).

Conclusions: Young recipient age and KC were associated with a better graft survival. Graft endothelial density and preservation time had no impact on graft survival. PBK, low vision at baseline and year 1, frequent GREs, and additional interventions during surgery had a negative impact on graft survivals.