The effect of alphaMSH analogues on rat bones

Melanocortin is the downstream mediator of leptin signaling and absence of leptin signaling in ob/ob and db/db mice revealed the enhancement of bone formation through the central regulation. While alpha-melanocyte-stimulating hormone (alphaMSH) inhibits the secretion of interleukin-1alpha and tumor necrosis factor-alpha from the inflammatory cells, alphaMSH can also enhance clonal expansion of pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the effect of melanocortin on bones. alphaMSH analogues [(6)His]alphaMSH-ND and [(6)Asn]alphaMSH-ND were synthesized and the radio-ligand receptor binding- and cyclic AMP generating activity were analyzed in China Hamster Ovary cell line over- expressing melanocortin receptors. The EC(50) of [(6)His]alphaMSH-ND measured from melanocortin-1, 3, 4 and 5 receptors were 0.008 +/- 0.0045, 1.523 +/- 0.707, 0.780 +/- 0.405, and 250.320 +/- 42.234 nM, respectively, and the EC(50) of [(6)Asn]alphaMSH-ND were 16.8 +/- 6.94, 271.8 +/- 21.95, 8.0 +/- 1.21, and 1132.5 +/- 635.46 nM, respectively. Four weeks after the subcutaneous injection of the analogues, the body weights in the [(6)His]alphaMSH-ND and the [(6)Asn]alphaMSH-ND treated groups (346.0 +/- 20.63 g vs. 350.0 +/- 13.57 g) were lower than that of the vehicle treated group (375.8 +/- 17.31 g, p < 0.05). There was no difference in the total femoral BMD measured by dual x-ray absorptiometry among the three groups. Among the three groups, there were no differences in the total numbers of crystal violet positive- or alkaline phosphatase positive colonies, in the expression of Receptor Activator of Nuclear Factor Kappa-B ligand on the tibia and the total number of multinucleated osteoclast-like cells differentiated from primary cultured bone marrow cells. From the above results, no evidence of bone gain or loss was found after treatment of the alphaMSH analogues peripherally.     

Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.     

Hypoglycemic activity of medicinal plants

The hypoglycemic activity of water extracts of fifty six medicinal plants were evaluated in the streptozotocin-induced diabetic mice. Twelve medicinal plants have significantly antidiabetic activity; Mori Radicis Cortex, Kwang Fang Chi Radix, Paeoniae Radix, Eugeniae Flos, Atractylodis Rhizoma, Ophiopogonis Tuber, Rosae multiflorae Fructus, Glycyrrhizae Radix, Tetrapanacis Medulla, Bigno, Forsythiae Fructus and Sophorae Radix.     

Peritoneal Simple Mesothelial Cyst Misdiagnosed as a Gastric Subepithelial Tumor

Journal of Gastrointestinal Surgery - Peritoneal simple mesothelial cysts are very rare mesenteric cysts of mesothelial origin. A peritoneal simple mesothelial cyst may be misdiagnosed, even by...     

Use of N-butyl cyanoacrylate in the successful transcatheter arterial embolization of an arteriovenous fistula caused by blunt pelvic fracture: A case report and review of literature

Rationale:Traumatic arteriovenous fistulas (AVFs) of the pelvis are uncommon and present with a variety of clinical manifestations; their detection may be difficult. An endovascular approach is usually the first choice of treatment, because surgical intervention is complicated due to the location of the lesions.Patient concerns:A 68-year-old man was admitted with severe pelvic pain following a fall.Diagnosis:A pelvic bone fracture (Young and Burgess Classification, lateral compression type II) was revealed on pelvic computed tomography (CT), while a pelvic sidewall hematoma, unaccompanied by any vascular injury, was detected on multidetector CT.Interventions:Pelvic angiography revealed an AVF between the internal iliac artery and vein, which was undetected by MDCT. The AVF was successfully treated using transcatheter arterial embolization (TAE) with n-butyl cyanoacrylate (NBCA).Outcomes:The patient recovered well and was discharged 4 weeks later. No complications were noted at the 8-month follow-up.Lessons:AVF may occur as a complication of blunt pelvic bone fracture. A high index of suspicion, angiography, and prompt diagnosis resulted in the successful management of our patient who presented with risk factors. Furthermore, TAE using NBCA enables a minimally invasive and effective treatment of traumatic pelvic AVF.     

Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity

Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described.Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity.Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induced nephrotoxicity. Morphological and flow cytometric analyses revealed that HK-2 cells actively phagocytized lead-exposed erythrocytes, which was associated with phosphatidylserine (PS) externalization on the erythrocyte membrane and generation of PS-bearing microvesicles. Increased oxidative stress and up-regulation of nephrotoxic biomarkers, such as NGAL, were observed in HK-2 cells undergoing erythrophagocytosis. Moreover, TGF-β, a marker of fibrosis, was also significantly up-regulated. We examined the significance of erythrophagocytosis in lead-induced nephrotoxicity in rats exposed to lead via drinking water for 12 weeks. We observed iron deposition and generation of oxidative stress in renal tissues of lead-exposed rats, as well as the histopathological alterations such as tubulointerstitial lesions, fibrosis, and up-regulation of KIM-1, NGAL, and TGF-β.Conclusions: Our data strongly suggest that erythrophagocytosis and subsequent iron deposition in renal tubular cells could significantly enhance nephrotoxicity following lead exposure, providing insight on lead-associated kidney damages.Citation: Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, Lim KM, Chung JH. 2015. Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: possible role in lead-induced nephrotoxicity. Environ Health Perspect 123:120–127; http://dx.doi.org/10.1289/ehp.1408094     

Diagnostic values of F-18 FDG PET or PET/CT,CT, and US for Preoperative Lymph Node Staging in Thyroid Cancer: A Network Meta-Analysis

ObjectiveThis study compared the diagnostic performance of three different imaging modalities for preoperative lymph node (LN) staging in thyroid cancer patients, using a network meta-analysis (NMA).MethodsPubMed and Embase were searched to identify studies evaluating the performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET or PET/CT), computed tomography (CT), and ultrasonography (US) for preoperative LN staging in thyroid cancer patients. The NMA included both patient- and lesion-based analyses. The surface under the cumulative ranking curve (SUCRA) values was used to decide on the most effective diagnostic method.ResultsA total of 3,571 patients from 19 direct comparison studies using three different imaging modalities for preoperative LN staging in thyroid cancer patients were included. US showed the highest SUCRA values for positive predictive values (PPV), negative predictive values (NPV), and accuracy in detection of all cervical LN metastasis. F-18 FDG PET or PET/CT and US showed the highest SUCRA values for PPV and sensitivity, respectively, for central LN, and the highest SUCRA value of specificity and sensitivity, respectively, for lateral LN.ConclusionThe results from this NMA indicate that F-18 FDG PET or PET/CT, CT, and US have complementary diagnostic roles for preoperative staging in thyroid cancer patients.Advances in knowledgeUsing NMA, we comprehensively compared the different diagnostic values and limitations of F-18 FDG PET or PET/CT, CT, and US for the preoperative LN staging in thyroid cancer patients.     

A New Asymmetric Directional Microphone Algorithm With Automatic Mode‐Switching Ability for Binaural Hearing Support Devices

For hearing support devices, it is important to minimize the negative effect of ambient noises for speech recognition but also, at the same time, supply natural ambient sounds to the hearing‐impaired person. However, conventional fixed bilateral asymmetric directional microphone (DM) algorithms cannot perform in such a way when the DM‐mode device and a dominant noise (DN) source are placed on the same lateral hemisphere. In this study, a new binaural asymmetric DM algorithm that can overcome the defects of conventional algorithms is proposed. The proposed algorithm can estimate the position of a specific DN in the 90°–270° range and switch directional‐ and omnidirectional‐mode devices automatically if the DM‐mode device and the DN are placed in opposite lateral hemispheres. Computer simulation and KEMAR mannequin recording tests demonstrated that the performance of the conventional algorithm deteriorated when the DM‐mode device and the DN were placed in the opposite hemisphere; in contrast, the performance of the proposed algorithm was consistently maintained regardless of directional variations in the DN. Based on these experimental results, the proposed algorithm may be able to improve speech quality and intelligibility for hearing‐impaired persons who have similar degrees of hearing impairment in both ears.