Contribution of estrogen receptor subtypes,ERα, ERβ, and GPER1 in rapid estradiol‐mediated enhancement of hippocampal synaptic transmission in mice

Estradiol rapidly modulates hippocampal synaptic plasticity and synaptic transmission; however, the contribution of the various estrogen receptors to rapid changes in synaptic function is unclear. This study examined the effect of estrogen receptor selective agonists on hippocampal synaptic transmission in slices obtained from 3–5‐month‐old wild type (WT), estrogen receptor alpha (ERαKO), and beta (ERβKO) knockout female ovariectomized mice. Hippocampal slices were prepared 10–16 days following ovariectomy and extracellular excitatory postsynaptic field potentials were recorded from CA3‐CA1 synaptic contacts before and following application of 17β‐estradiol‐3‐benzoate (EB, 100 pM), the G‐protein estrogen receptor 1 (GPER1) agonist G1 (100 nM), the ERα selective agonist propyl pyrazole triol (PPT, 100 nM), or the ERβ selective agonist diarylpropionitrile (DPN, 1 µM). Across all groups, EB and G1 increased the synaptic response to a similar extent. Furthermore, prior G1 application occluded the EB‐mediated enhancement of the synaptic response and the GPER1 antagonist, G15 (100 nM), inhibited the enhancement of the synaptic response induced by EB application. We confirmed that the ERα and ERβ selective agonists (PPT and DPN) had effects on synaptic responses specific to animals that expressed the relevant receptor; however, PPT and DPN produced only a small increase in synaptic transmission relative to EB or the GPER1 agonist. We demonstrate that the increase in synaptic transmission is blocked by inhibition of extracellular signal‐regulated kinase (ERK) activity. Furthermore, EB was able to increase ERK activity regardless of genotype. These results suggest that ERK activation and enhancement of synaptic transmission by EB involves multiple estrogen receptor subtypes. © 2015 Wiley Periodicals, Inc.     

Neuropathic Pain After Spinal Cord Injury: Challenges and Research Perspectives

Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that remains difficult to treat because underlying mechanisms are not yet fully understood. In part, this is due to limitations of evaluating neuropathic pain in animal models in general, and SCI rodents in particular. Though pain in patients is primarily spontaneous, with relatively few patients experiencing evoked pains, animal models of SCI pain have primarily relied upon evoked withdrawals. Greater use of operant tasks for evaluation of the affective dimension of pain in rodents is needed, but these tests have their own limitations such that additional studies of the relationship between evoked withdrawals and operant outcomes are recommended. In preclinical SCI models, enhanced reflex withdrawal or pain responses can arise from pathological changes that occur at any point along the sensory neuraxis. Use of quantitative sensory testing for identification of optimal treatment approach may yield improved identification of treatment options and clinical trial design. Additionally, a better understanding of the differences between mechanisms contributing to at- versus below-level neuropathic pain and neuropathic pain versus spasticity may shed insights into novel treatment options. Finally, the role of patient characteristics such as age and sex in pathogenesis of neuropathic SCI pain remains to be addressed.     

Are executive skills primarily mediated by the prefrontal cortex in childhood? Examination of focal brain lesions in childhood

Introduction

Based on the study of adults with brain insult, traditional localizationist views have argued that executive skills are primarily mediated by prefrontal cortex. It remains unclear whether a similar pattern of localization exists in childhood.

Methods:

To investigate this hypothesis, we compared the performance of children, aged 7–16 years, with radiological evidence of brain pathology. The sample was divided according to lesion location as follows: frontal pathology (n = 38), extra-frontal pathology (n = 20), generalized pathology (n = 21) and healthy controls (n = 40). Using a multidimensional model of executive function described by Anderson (2002) and [Anderson, 1998] , [Anderson et?al., 2001c] and [Anderson et?al., 2001d] ), these groups were compared on a range of executive function domains including: attentional control, goal setting, cognitive flexibility, and information processing. Additional, non-executive measures were also administered.

Results

Contrary to adult lesion-based studies, there was little differentiation in executive processes between frontal and extra-frontal groups.

Conclusions

These results provide support for contemporary models which propose a distributed, but integrated neural network for executive skills, suggesting that the integrity of the entire brain is necessary for adequate executive functions in childhood. Further, focal lesions to any brain region during development may render children vulnerable to a range of executive deficits that would not normally be expected following similar pathology in adulthood.     

Common allergens in shoe dermatitis: our experience in Lahore,Pakistan

BACKGROUND: Shoe dermatitis is a form of contact dermatitis resulting from exposure to shoes. Different chemicals, in conjunction with a hot and humid environment within the shoe, give rise to allergic or irritant dermatitis. Allergic shoe dermatitis is commonly caused by constituents of rubber, leather, adhesives, and rarely by linings and dyes. AIM: To determine the frequency of various allergens in shoe dermatitis in our patients. METHODS: One hundred and nine patients suspected of having contact dermatitis due to shoe allergens were included. All patients were patch tested with the Shoe series and European Standard series. Patches were applied on the upper back and removed after 48 h. Results were read at 48, 72, and 120 h and interpreted according to International Contact Dermatitis Research Group (ICDRG) criteria. RESULTS: Of the 119 patients, 87 (73%) reacted positively to various allergens, 48% of whom showed polysensitivity. Glues (33.6%), particularly para-tert-butylphenol formaldehyde resin (PTBP-FR) (26.9%), were the leading cause of shoe dermatitis. Other allergens were leather chemicals (26.4%), potassium dichromate (16.18%), rubber allergens (7.6%), and dyes (7.6%). Shoe scrapings tested positive in 26.3% of patients. Other common allergens were nickel sulfate (22.7%), neomycin sulfate (10.1%), and cobalt chloride (8.4%). CONCLUSIONS: Considering the diversity of allergens, all patients presenting with shoe dermatitis should be patch tested with the Shoe series and a standard series to determine the etiologic allergens.     

Periodontal Status and High‐Sensitivity C‐Reactive Protein Levels in Polycystic Ovary Syndrome With and Without Medical Treatment

Background: Recently, some studies have revealed the effect of polycystic ovary syndrome (PCOS) on gingival inflammation. This cross‐sectional study attempts to assess the periodontal status and systemic inflammation of women receiving medical treatment for PCOS and women newly diagnosed with PCOS. Methods: A total of 126 participants comprising 41 newly diagnosed patients with PCOS (PCOS‐N), 45 patients with PCOS on medical treatment (PCOS‐MT), and 40 systemically healthy controls (control group [CG]) were examined. Periodontal parameters, anthropometric parameters, and serum levels of high‐sensitivity C‐reactive protein (hsCRP) were recorded. Results: Women with newly diagnosed PCOS had increased sites with bleeding on probing (BOP), probing depth, clinical attachment level (CAL), waist circumference (WC), hsCRP, and prevalence of periodontitis compared with control and PCOS‐MT groups (P ≤0.05). On partial correlation analysis after controlling for confounders, BOP and CAL correlated positively and significantly with hsCRP (P = 0.01 and P = 0.005). Multivariate linear regression analysis revealed that BOP and CAL (dependent variable) (P = 0.009/R² = 0.05 and P = 0.005/R² = 0.07, respectively) had significant association with hsCRP. Furthermore, hsCRP, when considered as outcome, also exhibited association with CAL and WC (P = 0.002/R² = 0.07 and P = 0.04/R² = 0.106). Logistic regression analysis demonstrated that the PCOS‐N group had 2.88 times increased likelihood of having moderate periodontitis (adjusted odds ratio 2.88, 95% confidence interval 1.18 to 6.98). Conclusions: Women with newly diagnosed PCOS may have increased prevalence and likelihood for periodontitis, with higher measures of periodontal inflammation and breakdown than those on medical treatment for PCOS and systemically healthy females. Furthermore, periodontal breakdown might depend on systemic inflammation and vice versa.     

Gender differences in the associations between past-year gambling problems and psychiatric disorders

Background Psychiatric disorders frequently co-occur with pathological gambling. The extent to which co-occurence extends to subsyndromal levels of gambling or differs between women and men is incompletely understood. Aim To examine whether the association between psychiatric disorders and past-year gambling problems is stronger in women than men. Methods Data from the national epidemiological survey of alcoholism and related disorders (NESARC) (n = 43,093) were analyzed. Results Increasing severity of past-year gambling problems was associated with increasing odds of most past-year Axis I and lifetime Axis II disorders, regardless of gender. Associations between gambling problems and major depression, dysthymia, panic disorder, and nicotine dependence were statistically stronger in women than in men. Conclusions A severity-related association exists between past-year gambling problems and psychiatric disorders. The stronger associations in women suggest that gambling research, prevention and treatment efforts consider gender differences.     

Total hip arthroplasty with shortening osteotomy in congenital major hip dislocation sequelae

We retrospectively evaluated the postoperative results of total hip arthroplasty (THA) in patients presenting with Crowe group IV dislocated hips. Overall, results were compared with regard to the type of osteotomy performed (Z or oblique) to define the correct indications for surgical technique and choice of prosthetic implant. Thirty-three subtrochanteric shortening and derotational osteotomies in primary THA were performed in 26 patients secondary to congenital hip dislocation. A Z osteotomy was performed in 14 cases and an oblique osteotomy in 19. The surgical approach was direct lateral, and surgery was aimed at restoring the anatomic hip center. Femoral and acetabular fixation was uncemented. The most used stem was the S-ROM (DePuy, Leeds, United Kingdom), and the couplings used were ceramic-ceramic (7 cases), ceramic-polyethylene (3 cases), metal-polyethylene (15 cases), and metal-metal (3 cases). Mean follow-up was 88±45 months. According to the Merle D'Aubigné score, the overall clinical results were good in 23 cases, satisfactory in 6, and fair in 4. Union of the osteotomy occurred in 97% of cases, and the mean time required for osteotomy union was 6±2 months without significant differences between Z and oblique osteotomies. At last follow-up, there was loosening of 1 cup and 1 stem, and revision was necessary. Twelve percent of patients experienced postoperative dislocation and 9% developed neuropraxia of the femoral nerve. The clinical and radiological results were similar in both groups, with a high rate of pain relief, an improvement in limb-length discrepancy, and reduced limping, leading to a smaller or no insole. Currently, the more complex Z osteotomy has been abandoned, because a modular stem prosthesis with metaphyseal sleeve allows the oblique osteotomy to be used with an easier and shorter surgical procedure.     

Canine prostate stimulates osteoblast function using the endothelin receptors

BACKGROUND: Bone metastases are common in humans and dogs with late-stage prostate cancer. A unique feature of prostate cancer metastases is new bone formation at metastatic sites ("osteoblastic metastases"). Many carcinomas that metastasize to bone cause bone destruction, not new bone formation. The mechanisms by which prostate cancer induces bone formation at sites of bone metastasis are not well understood. We hypothesized that stimulation of osteoblasts by prostate tissue at metastatic sites was due to the paracrine actions of growth factors produced by prostate epithelial cells. METHODS: We have previously shown that normal canine prostate tissue induced new bone formation when implanted adjacent to the calvarium of nude mice. To complement this in vivo model, we developed an in vitro system of prostate-stimulated osteoblast function to investigate mechanisms of prostate-induced new bone formation. RESULTS: We found that treatment of cultured rat calvaria for 24 hr with proteins from normal dog prostate stimulated alkaline phosphatase activity in a dose-dependent manner 4-6 fold compared to controls. Stimulation began approximately 8 hr after treatment, and was diminished after 72 hr. Calvaria treated with homogenates of normal dog salivary gland, kidney, bladder, and muscle did not increase ALP activity. Pretreatment of the calvaria for 1 hr with endothelin antagonists, but not anti-parathyroid hormone-related protein (PTHrP) antibody or indomethacin, abrogated the stimulation of ALP. CONCLUSIONS: Our results indicated that osteoblast activation by canine prostate occurs via an endothelin-dependent mechanism, and that PTHrP or prostaglandin synthase-mediated pathways are likely not involved. This is a reliable, reproducible assay for determining the roles of molecules important in the activation of osteoblasts by the prostate.     

Serum protein profile studies of cervical cancers in monitoring of tumor response to radiotherapy using HPLC-LIF: A pilot study

ObjectiveExploration of the feasibility of serum protein profiles for monitoring tumor radioresponse in cervical cancers using HPLC-LIF system.Materials and methodsTwenty-one subjects were recruited in the study. Out of them 7 were healthy, 14 were cervical cancer patients who undertook fractionated radiotherapy (RT) with 2 Gy per fraction over 25 fractions, for 5 weeks followed by 2 applications of intracavitary brachytherapy once a week.Blood collected from above subjects was processed to obtain serum. Serum chromatograms of ‘normal’ (n=7) and conspicuous probes before RT (n=14, ‘malignant’) and 24 h after second fraction of RT (n=13, ‘2-RT’), were recorded using an In-house-built HPLC-LIF set-up. Data were analyzed in two approaches: (1) classical method using relative intensities of selected peaks, (2) principal component analysis (PCA).Clinical assessment of tumor radioresponse was carried out 4 months after first fraction of RT and the degree of the tumor shrinkage was determined as an index of radioresponsiveness (complete response (CR): 100% shrinkage, partial response (PR): ≥50% shrinkage, and no response (NR): ≤50% shrinkage) which was further correlated with the analysis of 2-RT serum chromatograms.ResultsNormal vs. malignant chromatograms demonstrated pronounced differences in the 800–1800 s region. Malignant vs. 2-RT chromatograms showed minute variations in the 1300–1800 s region. Our analysis, in both of the approaches, produced clear differentiation between ‘normal’ and ‘malignant’, whereas differentiation between ‘malignant’ and ‘2-RT’ was minimal. Clinical evaluation of the tumor radioresponse yielded that out of 13 patients (one patient discontinued the radiotherapy) ten showed CR, two showed PR and one NR. In case of prediction of tumor radioresponse, analysis of the 2-RT chromatograms produced only minor differentiation among CR, PR and NR groups.ConclusionProtein profiling of serum samples differentiated ‘normal’ from ‘malignant’, but could not differentiate ‘malignant’ from ‘2-RT’. Also this technique has limited application in prediction of tumor radioresponse.