Infection with varicella zoster virus (VZV) results in chicken pox and reactivation of VZV results in herpes zoster (HZ) or what is often referred to as shingles. Patients with HZ experience ...decreased motivation and increased emotional distress consistent with functions of the ventral tegmental area (VTA) of the brain. In addition, activity within the ventral tegmental area is altered in patients with HZ. HZ primarily affects individuals that are older and the VTA changes with age. To begin to determine if the VTA has a role in HZ symptoms, a screen of 10,000 genes within the VTA in young and old male rats was completed after injecting the whisker pad with VZV. The two genes that had maximal change were membrane progesterone receptors PAQR8 (mPRβ) and PAQR9 (mPRε). Neurons and non-neuronal cells expressed both PAQR8 and PAQR9. PAQR8 and PAQR9 protein expression was significantly reduced after VZV injection of young males. In old rats PAQR9 protein expression was significantly increased after VZV injection and PAQR9 protein expression was reduced in aged male rats versus young rats. Consistent with previous results, pain significantly increased after VZV injection of the whisker pad and aged animals showed significantly more pain than young animals. Our data suggests that PAQR8 and PAQR9 expression is altered by VZV injection and that these changes are affected by age.
The case report in this review illustrates an acute myocardial infarction in a young adult probably due to arterial thrombosis that can be attributed to a hypercoagulable state resulting from the ...nephrotic syndrome. Although rare, acute myocardial infarction should be considered in young adults presenting with chest pain. A detailed clinical history may help to identify the aetiology, and guide subsequent management, but diagnostic coronary angiography is essential. Careful risk factor modification and treatment of the underlying cause should reduce the incidence of recurrent cardiac events.
•Duchenne muscular dystrophy cardiomyopathy is diagnosed late, with worse outcomes.•Standard echocardiogram is less sensitive at detecting signs of cardiac dysfunction.•Cardiac magnetic resonance has ...more accuracy and reliability than echocardiography.•Cardiac magnetic resonance is underutilised in Duchenne muscular dystrophy.•Further research in physiological functional stress assessments is needed.
Duchenne Muscular Dystrophy is the most common paediatric neuromuscular disorder. Mutations in the DMD gene on the X-chromosome result in progressive skeletal muscle weakness as the main clinical manifestation. However, cardiac muscle is also affected, with cardiomyopathy becoming an increasingly recognised cause of morbidity, and now the leading cause of mortality in this group. The diagnosis of cardiomyopathy has often been made late due to technical limitations in transthoracic echocardiograms and delayed symptomatology in less mobile patients. Increasingly, evidence supports earlier pharmacological intervention in cardiomyopathy to improve outcomes. However, the optimal timing of initiation remains uncertain, and the benefits of prophylactic therapy are unproven. Current treatment guidelines suggest initiation of therapy once cardiac dysfunction is detected. This review focuses on new and evolving techniques for earlier detection of Duchenne muscular dystrophy-associated cardiomyopathy. Transthoracic echocardiography or cardiac magnetic resonance imaging performed under physiological stress (dobutamine or exercise), can unmask early cardiac dysfunction. Cardiac magnetic resonance imaging can define cardiac function with greater accuracy and reliability than an echocardiogram, and is not limited by body habitus. Improved imaging techniques, used in a timely fashion, offer the potential for early detection of cardiomyopathy and improved long-term outcomes.
Orofacial pain disorders are predominately experienced by women. Progesterone, a major ovarian hormone, is neuroprotective and antinociceptive. We recently reported that progesterone attenuates ...estrogen-exacerbated orofacial pain behaviors, yet it remains unclear what anatomical substrate underlies progesterone’s activity in the trigeminal system. Progesterone has been reported to exert protective effects through actions at intracellular progesterone receptors (iPR), membrane-progesterone receptors (mPR), or sigma 1 receptors (Sig-1R). Of these, the iPR and Sig-1R have been reported to have a role in pain. Progesterone can also have antinociceptive effects through its metabolite, allopregnanolone. Two enzymes, 5α-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD), are required for the metabolism of progesterone to allopregnanolone. Both progesterone and allopregnanolone rapidly attenuate pain sensitivity, implicating action of either progesterone at Sig-1R and/or conversion to allopregnanolone which targets GABAA receptors. In the present study, we investigated whether Sig-1 Rs are expressed in nociceptors within the trigeminal ganglia of cycling female rats and whether the two enzymes required for progesterone metabolism to allopregnanolone, 5α-reductase and 3α-hydroxysteroid dehydrogenase, are also present. Adult female rats from each stage of the estrous cycle were rapidly decapitated and the trigeminal ganglia collected. Trigeminal ganglia were processed by either fluorescent immunochemistry or western blotting to for visualization and quantification of Sig-1R, 5α-reductase, and 3α-hydroxysteroid dehydrogenase. Here we report that Sig-1Rs and both enzymes involved in progesterone metabolism are highly expressed in a variety of nociceptive sensory neuron populations in the female rat trigeminal ganglia at similar levels across the four stages of the estrous cycle. These data indicate that trigeminal sensory neurons are an anatomical substrate for the reported antinociceptive activity of progesterone via Sig-1R and/or conversion to allopregnanolone.
Recent studies have reported that the transient receptor potential V1 ion channel (TRPV1), a pain generator on sensory neurons, is activated and potentiated by NADPH oxidase-generated reactive oxygen ...species (ROS). ROS are increased by advanced oxidation protein products (AOPPs), which activate NADPH oxidase by upregulating Nox4 expression. Our previous studies reported that Euphorbia bicolor (Euphorbiaceae) latex extract induced peripheral analgesia, partly via TRPV1, in hindpaw-inflamed male and female rats. The present study reports that E. bicolor latex extract also can evoke analgesia via reduction of oxidative stress biomarkers and proinflammatory cytokines/chemokines in a rat model of orofacial pain. Male and female rats were injected with complete Freund’s adjuvant (CFA) into the left vibrissal pad to induce orofacial inflammation, and mechanical allodynia was measured by the von Frey method. Twenty-four hours later, rats received one injection of E. bicolor latex extract or vehicle into the inflamed vibrissal pad. Mechanical sensitivity was reassessed at 1, 6, 24, and/or 72 hours. Trigeminal ganglia and trunk blood were collected at each time point. In the trigeminal ganglia, ROS were quantified using 2′,7′-dichlorodihydrofluorescein diacetate dye, Nox4 protein was quantified by Western blots, and cytokines/chemokines were quantified using a cytokine array. AOPPs were quantified in trunk blood using a spectrophotometric assay. E. bicolor latex extract significantly reduced orofacial mechanical allodynia in male and female rats at 24 and 72 hours, respectively. ROS, Nox4, and proinflammatory cytokines/chemokines were significantly reduced in the trigeminal ganglia, and plasma AOPP was significantly reduced in the trunk blood of extract-treated compared to vehicle-treated rats. In vitro assays indicate that E. bicolor latex extract possessed antioxidant activities by scavenging free radicals. Together our data indicate that the phytochemicals in E. bicolor latex may serve as novel therapeutics for treating oxidative stress-induced pain conditions.
Although right ventricular (RV) dysfunction is an important complication in subjects with congenitally corrected transposition of the great arteries, its pathogenesis is poorly understood. We ...assessed the role of RV myocardial perfusion and found perfusion defects at rest in all 20 patients, involving 4.6 +/- 2.3 of a total of 12 segments; the extent of the resting perfusion defects correlated inversely with the RV ejection fraction.
Background Patients with systemic ventricles of right ventricular morphology are at high risk of contractile dysfunction, the cause of which has not been fully elucidated. Objective To assess whether ...ischaemia or infarction contributes to ventricular impairment in unoperated patients with uncomplicated congenitally corrected transposition of the great arteries (TGA) by studying myocardial perfusion and function. Setting Paediatric and adult congenital cardiac clinics of a tertiary referral centre. Patients Five patients with congenitally corrected TGA but without associated structural cardiac defects (aged 3.5 to 34 years). Interventions Maximal exercise stress testing using standard or modified Bruce protocols. Sestamibi (technetium-99m methoxy isobutyl isonitrile) scanning after isotope injection at maximal exercise and rest. Main outcome measures Maximum exercise capacity; right ventricular myocardial perfusion, regional wall motion, and thickening; right ventricular ejection fraction. Results The two youngest patients (3.5 and 11 years) had normal exercise capacity for age, while the others had reduced exercise performance. Sestamibi scanning showed reversible myocardial ischaemia in four patients and fixed defects indicating infarction in five. Irreversible defects were mostly associated with impaired wall motion and thickening. The ejection fraction was normal (65%) in the youngest patient but < 55% in the others (mean (SD) 47(11)%). Conclusions Patients with unoperated congenitally corrected TGA have a high prevalence of myocardial perfusion defects, with consequent abnormalities of regional wall motion and thickening, and impaired ventricular contractility. These data suggest that ischaemia and infarction are important in the pathogenesis of ventricular failure in this condition.
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