Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition

Background/aimCertain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse.MethodsHesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples.ResultsSingle-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles.ConclusionMefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.     

A novel approach for rapid screening of mitochondrial D310 polymorphism

Background  

Mutations in the mitochondrial DNA (mtDNA) have been reported in a wide variety of human neoplasms. A polynucleotide tract extending from 303 to 315 nucleotide positions (D310) within the non-coding region of mtDNA has been identified as a mutational hotspot of primary tumors. This region consists of two polycytosine stretches interrupted by a thymidine nucleotide. The number of cytosines at the first and second stretches are 7 and 5 respectively, according to the GeneBank sequence. The first stretch exhibits a polymorphic length variation (6-C to 9-C) among individuals and has been investigated in many cancer types. Large-scale studies are needed to clarify the relationship between cytosine number and cancer development/progression. However, time and money consuming methods such as radioactivity-based gel electrophoresis and sequencing, are not appropriate for the determination of this polymorphism for large case-control studies. In this study, we conducted a rapid RFLP analysis using a restriction enzyme, BsaXI, for the single step simple determination of 7-C carriers at the first stretch in D310 region.     

A schwannoma mimicing hypopharyngeal carcinoma

Hypopharyngeal schwannoma is quite rare, with only nine cases presented in the literature to our knowledge. The presentation itself requires a distinction from malignant hypopharyngeal disease, which is usually the initial diagnosis. A transcervical approach and laryngomicrosurgery are two possible operating methods for the treatment of hypopharyngeal schwannoma. The selection of the surgical method depends on the size of the tumor. For this case, we preferred the transcervical approach without tracheotomy. In contrast to previous case reports, we were unable to trace the original nerve.     

Radiological outcome of proximal femoral varus osteotomy for the treatment of lateral pillar group-C Legg-Calvé-Perthes disease

Results from 26 hips of 24 Legg-Calvé-Perthes disease patients were evaluated retrospectively. There were 22 male and two female patients in the study group. The mean age of the patients was 8.3 years and the mean follow-up was 13.03 years. All the patients were older than 6 years of age and all of them had lateral pillar group C hips. The patients were treated with intertrochanteric uniplanar varus osteotomy. All the patients were mature at the time of the last evaluation. Radiological end results were evaluated according to Stulberg's classification. Six hips healed with spherical congruency (Stulberg class 1 or 2), 19 with aspherical congruency (Stulberg class 3 or 4) and one with aspherical incongruency (Stulberg class 5). Six of 14 hips treated before 9 years of age healed with spherical congruency but all hips treated after 9 years of age healed with Stulberg class 3, 4 or 5 results. Trochanteric overgrowth was evident in 20 hips. The results of this radiological outcome study showed that Herring class C hips treated with proximal femoral varus osteotomy had a poor outcome, especially after 9 years of age in this group of patients.     

Squamous cell carcinoma arising from a fibroepithelial polyp

Fibroepithelial polyps (FEPs) are among the most common benign skin lesions treated frequently without submitting for histologic examination since malignant degeneration is exceedingly rare. In this case report, we describe an aggressive gross squamous cell carcinoma mass arising from a large pedunculated-type FEP located at the lower limb, which, to our knowledge, has not been reported yet.     

Endothelin receptor antagonist bosentan improves survival in a murine caecal ligation and puncture model of septic shock

The role of endothelin peptides was evaluated on survival and organ injury in a model of polymicrobial sepsis, induced by caecal ligation and puncture with particular emphasis on the timing of the administration of its blocker bosentan in Swiss albino mice (20-40 g). The cardiovascular response pattern in this experimental model was characterized by an early, "hyperdynamic" phase starting at 5 h, followed by a late but "hypodynamic" phase that commence after 20 h, provided that the animals are "resuscitated" by injecting 1 ml of saline i.p. at the end of the surgery. However, if saline resuscitation is omitted, then only hypodynamic pattern is observed starting at 5 h without any hyperdynamic phase. Thus, mice were first allocated into saline-resuscitated or unresuscitated groups and endothelin receptor antagonist bosentan (30 mg kg(-1), i.p., either 5 or 20 h after caecal ligation and puncture) was then administered. The control animals received the solvent of bosentan (i.e., saline: %0.9 NaCl, w/v). The survival rates in each group (n=14) were recorded over the following 144 h. In unresuscitated mice, the overall survival at 144 h was 14.3% in controls while bosentan treatment at 5 h (78.6%, P=0.0018) or 20 h (64.3%, P=0.0183) have both significantly improved the survival. However, in saline-resuscitated mice, bosentan administered at 20 h has significantly improved the survival (71.4%, P=0.0213) while its administration at 5 h has yielded exactly the same percent of survival (i.e., 21.4%) as observed in control animals. The beneficial effects of bosentan in preventing the tissue injury due to caecal ligation and puncture were also observed histopathologically in liver, spleen and kidney. Therefore, we concluded that the blockade of endothelin receptors by using bosentan during the later (hypodynamic) stages of septic shock is a promising therapeutic manoeuvre.     

The role of psychological factors in alopecia areata and the impact of the disease on the quality of life

BACKGROUND: The role of psychological factors in the pathogenesis of alopecia areata (AA) has long been the subject of debate. Numerous studies have provided controversial results. AIM: This case-control study was undertaken to determine the significance of stressful life events and other psychological factors in the etiopathogenesis of AA. The impact of the disease on the quality of life was also assessed. METHODS: Fifty-two adult patients (18 females and 34 males) diagnosed with AA and 52 age- and sex-matched individuals selected from hospital staff without any hair loss (control group) were evaluated using the major life events scale, Beck depression and Beck anxiety inventories, and the Short Form-36 health survey (SF-36). In addition, comparison was performed between two patient groups created according to whether or not they linked emotional trauma with their AA attack. RESULTS: There was no statistically significant difference between the patient and control groups with regard to the total scores of stressful major life events, depression, and anxiety. Of the eight subscales on SF-36, vitality and mental health scores were higher in the control group, whereas social functioning scores were higher in the patients. The total number of stressful life events was higher in patients who attributed their disease to a stressful life event than in those who did not. CONCLUSIONS: It appears unlikely that anxiety and depression play a major role in the etiopathogenesis of AA, but stressful life events may act as a trigger in the onset and/or exacerbation of the disease. Furthermore, AA seems to have a partly negative impact on the health-related quality of life.     

Elevated serum TNF-alpha levels in normal-weight women with polycystic ovaries or the polycystic ovary syndrome

OBJECTIVE: To compare the serum tumor necrosis factor-alpha (TNF-alpha) levels in nonobese women with those in women with polycystic ovaries (PCO) and polycystic ovary syndrome (PCOS) and healthy controls. STUDY DESIGN: Twenty-one sonographically and biochemically diagnosed women with PCOS, 19 with PCO and 14 healthy women were recruited for the study. Serum TNF-alpha levels were measured in all three groups. Insulin and glucose serum concentrations were analyzed before and after a 75-g oral glucose tolerance test in all samples. The serum TNF-alpha, glucose and insulin levels were compared in PCOS, PCO and controls. RESULTS: Serum TNF-alpha levels were similar in the PCOS and PCO groups (23.67 +/- 5.58 and 13.58 +/- 1.34 pg/mL, respectively) and significantly higher than in the control group. Serum TNF-alpha levels did not significantly correlated with body mass index, serum total testosterone, LH, DHEAS, fasting glucose and fasting insulin levels or glucose and insulin area under the curve values in the three groups. CONCLUSION: We found similar TNF-alpha levels in patients with PCOS and with PCO; however, there was no correlation between the TNF-alpha and insulin, glucose and androgen levels in the study.