Distribution and neurochemical characterization of protein kinase C-theta and -delta in the rodent hypothalamus.

PKC-theta (PKC-θ), a member of the novel protein kinase C family (nPKC), regulates a wide variety of functions in the periphery. However, its presence and role in the CNS has remained largely unknown. Recently, we demonstrated the presence of PKC-θ in the arcuate hypothalamic nucleus (ARC) and knockdown of PKC-θ from the ARC protected mice from developing diet-induced obesity. Another isoform of the nPKC group, PKC-delta (PKC-δ), is expressed in several non-hypothalamic brain sites including the thalamus and hippocampus. Although PKC-δ has been implicated in regulating hypothalamic glucose homeostasis, its distribution in the hypothalamus has not previously been described. In the current study, we used immunohistochemistry to examine the distribution of PKC-θ and -δ immunoreactivity in rat and mouse hypothalamus. We found PKC-θ immunoreactive neurons in several hypothalamic nuclei including the ARC, lateral hypothalamic area, perifornical area and tuberomammillary nucleus. PKC-δ immunoreactive neurons were found in the paraventricular and supraoptic nuclei. Double-label immunohistochemisty in mice expressing green fluorescent protein either with the long form of leptin receptor (LepR-b) or in orexin (ORX) neurons indicated that PKC-θ is highly colocalized in lateral hypothalamic ORX neurons but not in lateral hypothalamic LepR-b neurons. Double-label immunohistochemistry in oxytocin-enhanced yellow fluorescent protein mice or arginine vasopressin-enhanced green fluorescent protein (AVP-EGFP) transgenic rats revealed a high degree of colocalization of PKC-δ within paraventricular and supraoptic oxytocin neurons but not the vasopressinergic neurons. We conclude that PKC-θ and -δ are expressed in different hypothalamic neuronal populations.

Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse.

The melanocortin system is involved in hypothalamic regulation of energy homeostasis. The melanocortin-4 receptor (MC4R) has been linked to both obesity and reproductive dysfunction. Deletion of the MC4R from the mouse genome has resulted in phenotypes including adult onset obesity, hyperphagia, and difficulty in reproducing when homozygote parents are bred. Additionally, polymorphisms of the human MC4R have been identified in morbidly obese children and adults. Herein, we have identified that voluntary exercise, provided via the presence of a running wheel, impedes the monogenetic obesity (at 20 weeks of age running wheel housed body weight=31+/-1.8 g versus conventionally housed body weight=41+/-2.3 g, a 25% decrease in body weight p<0.01), hyperphagia (average cumulative food intake is not statistically different than wild type mice housed in running wheel cages), and reproductive dysfunction phenotypes associated with the MC4R knockout mice housed by conventional means. These data demonstrate the novel finding that voluntary exercise at a young age may hinder genetically induced obesity.

The melanocortin pathway: effects of voluntary exercise on the melanocortin-4 receptor knockout mice and ACTH(1-24) ligand structure activity relationships at the melanocortin-2 receptor.

The melanocortin pathway consists of endogenous agonists, antagonists, G-protein coupled receptors, and ancillary proteins that mediate the function of the endogenous antagonists. The melanocortin-4 receptor (MC4R) is involved in the regulation of obesity and the melanocortin-2 receptor (MC2R) is involved in the regulation of steroidogenesis. Herein, we present the effects of voluntary exercise on the MC4R knockout mice in terms of bypassing the morbid obesity and hyperphagia phenotypes associated with this genetic obesity model. Additionally, a systematic truncation study of the adrenocorticotropin hormone (ACTH 1-24) has been performed and characterized at the cloned MC2R.

Aural papillomatosis--treatment with the carbon dioxide laser.

Aural papillomatosis has been infrequently reported in the English literature. It is a condition which can be very difficult to treat. We present the first reported case of aural papillomatosis successfully treated with the CO2 laser.

Maxillary sinusitis in children with otitis media with effusion.

Sinus radiographs have been carried out on 240 new cases of childhood otitis media with effusion (OME). When the films were suggestive of infection, maxillary sinus washouts were carried out as part of the surgical treatment. Abnormal X-rays were obtained in 28 per cent of the study group, but only 16 cases (seven per cent) of sinus infection were confirmed on antral lavage. In those with positive washouts, there was an apparent relationship between the findings in the maxillary sinuses and middle ears of the same side in some of the cases. There was also evidence of improvement of the middle ear disease when the sinus infection was successfully treated. It does not appear that sinus infection is an important cause of OME, though it may be relevant in a small number of cases.

Relapsing polychondritis--a study of four cases.

Four case reports of relapsing polychondritis, (RP), are presented, together with a literature review and management suggestions. There are approximately 211 reported cases in world literature making RP an uncommon condition associated with high morbidity and mortality rates. The key to the management of RP is based on accurate and early diagnosis though the ideal medical regimen has yet to be elucidated.

Oncocytic papillary cystadenomatosis of the larynx.

Symptomatic oncocytic disease of the larynx is rare. Review of the world literature reveals that isolated, symptomatic cases of oncocytoma of the larynx have been previously reported to involve discrete sites usually the laryngeal ventricles and vestibular folds. A unique case of multifocal cystic oncocytic hyperplasia necessitating laryngectomy is reported. CT scan of the larynx suggested destruction of the cartilage. Malignant histological features were not present. This report raises the question whether previously described cases of oncocytoma of the larynx also had diffuse involvement. If oncocytosis is a diffuse process then it is suggested that patients should be kept under review for recurring lesions.

Infection of the neck spaces: a present day complication.

Although advances in antibiotic therapy have made adult neck space infections an uncommon event, it is essential to bear them in mind when treating oro-dental and oro-pharyngeal sepsis, as they can often progress with life threatening sequelae. Three cases of neck space infection as a consequence of dental infection, pharyngitis and peritonsillar abscess are presented. The management of a potentially compromised airway is of paramount importance in the immediate treatment of neck space sepsis.

Distribution of topical antibiotic preparations in mastoid cavities.

Topical antibiotic preparations are widely prescribed in the treatment of infected mastoid cavities with no knowledge of the distribution of the preparation within the cavity. This study ascertains the distribution of drop and spray preparations within mastoid cavities and suggests methods of delivery to maximize coverage.