Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population.

BACKGROUND: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population. METHODS: The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorphism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients. RESULTS: The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2 diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population. CONCLUSIONS: Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPARgamma-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes.     

Clinical trials update from the European Society of Cardiology Meeting 2010: SHIFT, PEARL-HF, STAR-heart, and HEBE-III

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the annual meeting of the European Society of Cardiology held in Stockholm in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The SHIFT study supports the use of ivabradine in patients with HF due to left ventricular systolic dysfunction and resting sinus rhythm rate ≥70 b.p.m. despite treatment with beta-blockers or where beta-blockers are contra-indicated. Results from PEARL-HF suggest that the potassium binding polymer RLY5016 may be useful for both prevention and treatment of hyperkalaemia in HF patients with or without concomitant chronic kidney disease. The STAR-heart study provides encouraging observational data about the potential for intracoronary stem cell transplantation in patients with HF. Results from HEBE-III showed no effect of erythropoietin on ejection fraction measured 6 weeks post-MI; although there were fewer cardiovascular events in patients assigned to erythropoietin, the study was too small to provide conclusive evidence of effect.     

Targeting oxidative stress component in the therapeutics of epilepsy

The role of free radical-mediated reactions in human neuropathology continues to attract significant interest. Oxidative injury produced by free radicals may play a role in the initiation and progression of epilepsy and, therapies aimed at reducing oxidative stress may ameliorate tissue damage and favorably alter the clinical course. The prevalence of epilepsy increases with age, and mitochondrial oxidative stress is a leading mechanism of aging and age-related degenerative disease, signifying a further involvement of mitochondrial dysfunction in seizure generation. Oxidative stress occurs when the generation of reactive oxygen species in a system exceeds the body's ability to neutralize and eliminate them, thus creating an imbalance or over abundance of free radicals. Therefore, it is imperative to maintain oxidative balance and control in the brain, and this is tightly regulated by antioxidants. In the last two decades, there has been an explosive interest in the role of antioxidants or neuroprotectants in clinical as well as experimental models of epilepsy. In this regard, the present review is intended to discuss the current state of knowledge pertaining to neuroprotection in epileptic conditions by employing diverse chemical agents including conventional as well as novel anti-epileptic drugs, and to highlight the efficacy of distinct neuroprotective strategies for preventing or treating epilepsy.     

Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice

Abstract: This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6‐bis‐(4‐hydroxy‐3‐methoxybenzylidene)cyclohexanone (BHMC), using chemical‐ and thermal‐induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose‐related inhibition in the acetic acid‐induced abdominal constriction test in mice with an ID₅₀ of 0.15 (0.13–0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin‐induced paw licking test with an ID₅₀ of 0.35 (0.27–0.46) mg/kg and 0.07 (0.06–0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot‐plate test. Moreover, the antinociceptive effect of the BHMC in the formalin‐induced paw licking test and the hot‐plate test was antagonized by pre‐treatment with the non‐selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID₅₀ of 0.66 (0.41–1.07) mg/kg and 0.42 (0.38–0.51) mg/kg, respectively. Finally, it was also shown that BHMC‐induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.     

Does COLIA1 SP1-binding site polymorphism predispose women to pelvic organ prolapse?

Introduction and hypothesis  COLIA1 polymorphism is associated with increased risk for stress urinary incontinence. We hypothesize that a similar association exists with pelvic organ prolapse (POP). Methods  Patients with advanced prolapse and healthy controls were evaluated by interview, validated questionnaires, and pelvic examination. DNA was extracted from peripheral blood, and polymerase chain reaction was performed to determine the presence or absence of the polymorphism. Power calculation indicated the need for 36 patients in each arm. Results  The prevalence of the polymorphic heterozygous genotype (GT) in the study and control groups was 33.3% and 19.4%, respectively, leading to an odds ratio of 1.75. This difference, however, did not reach statistical significance (p = 0.27). Conclusions  The COLIA1 polymorphism was not significantly associated with increased risk for POP.     

Transient anesthetic-induced worsening of existing left-sided weakness in a patient undergoing elective anterior cervical discectomy

The differential diagnosis of new or worsening focal neurologic deficits on emergence from anesthesia is broad. Cerebral ischemia or hemorrhage, focal seizures, and acute metabolic abnormalities can all result in similar neurologic findings. Intravenously administered anesthetic agents also have been reported to cause new or worsening focal neurologic deficits in patients with a history of preexisting deficits. A patient who suffered such a reversible deficit related to anesthesia is presented.     

Spinal Glioblastoma Multiforme: Unusual Cause of Post-Traumatic Tetraparesis

Background/Objective:

Glioblastoma multiforme (GBM) is the most common glial cell tumor of the adult brain. However, primary GBM of the spinal cord is a rare condition.

Methods:

Case report.

Results:

A young man presented with acute onset quadriparesis after a whiplash injury. A magnetic resonance scan showed the typical appearance of a high-grade intramedullary tumor with fusiform expansion of the entire cervical cord. Subtotal decompression and biopsy was done by posterior laminectomy, followed by external beam radiotherapy. Signs and symptoms improved after the completion of radiotherapy but did not resolve completely. Death caused by respiratory failure occurred 3 months later.

Conclusions:

This presentation of GBM of the cervical cord is rare; an intramedullary tumor should be considered when minor cervical trauma results in disproportionate neurologic deficit. To the best of our knowledge, this is the first reported case of spinal GBM with extensive pan-cervical involvement.     

Tarlov Cyst and Infertility

Background/Objective:

Tarlov cysts or spinal perineurial cysts are uncommon lesions. These are mostly incidental findings on magnetic resonance imaging or myelograms. The objectives of this study were to describe Tarlov cysts of the sacral region as a potential cause for retrograde ejaculations and review available management options.

Methods:

Case report and literature review.

Results:

A 28-year-old man presented with back pain and retrograde ejaculations resulting in infertility. After microsurgical excision of large perineurial cysts, back pain resolved, but semen quality showed only marginal improvement. Later, the couple successfully conceived by intrauterine insemination. To the best of our knowledge, this is the first reported case of Tarlov cyst associated with retrograde ejaculation and infertility.

Conclusions:

Despite being mostly asymptomatic and an incidental finding, Tarlov cyst is an important clinical entity because of its tendency to increase in size with time. Tarlov cysts of the sacral and cauda equina region may be a rare underlying cause in otherwise unexplained retrograde ejaculations and infertility. Microsurgical excision may be a good option in a select group of patients.     

Lipoblastoma--a rare paediatric foot tumour

Lipoblastoma, a rare benign tumour arising from embryonic fat, is usually found in areas of abundant adipose tissue. Various reports describe a predilection of lipoblastoma for sites with primitive adipose tissue such as axilla, neck, retroperitoneum and prevertebral soft tissue. The plantar aspect of the foot is an extremely rare site due to scarcity of fatty tissue. Differential diagnosis includes lipomas, fibromyxolipomas and liposarcomas. Age of presentation, chromosomal markers and histopathological examination help in arriving at final diagnosis. Radical surgeries are not advocated; however, complete excision is necessary to avoid recurrence.