Effects of Losartan,HO‐1 Inducers or HO‐1 Inhibitors on Erectile Signaling in Diabetic Rats

IntroductionActivation of the renin‐angiotensin system which is common in diabetes mellitus might affect heme oxygenase (HO‐1) gene expression.AimAssessment of the effects of administration of angiotensin II (Ang II) receptor antagonist (losartan) with HO‐1 inducer or inhibitor on erectile signaling in diabetic rats.Materials and MethodsSeventy male rats were divided equally into seven groups; healthy controls, streptozotocin‐induced diabetic rats, rats on citrate buffer, diabetic rats on losartan, diabetic rats on HO‐1 inducer (cobalt protoporphyrin [CoPP]), diabetic rats on losartan and CoPP, and diabetic rats on losartan and HO‐1 inhibitor (stannus mesoporphyrin [SnMP]).Main Outcome MeasureHO enzyme activity, HO‐1 gene expression, cyclic guanosine monophosphate (cGMP) assay, intracavernosal pressure (ICP), and cavernous tissue sinusoids surface area.ResultsHO‐1 gene expression, HO enzymatic activity, and cGMP were significantly decreased in the cavernous tissue of diabetic rats. These parameters were significantly elevated with the use of CoPP that restored the normal control levels of HO enzyme activity. Administration of losartan exhibited a significant enhancing effect on these parameters compared with the diabetic group, but not restored to the control levels, whereas administration of CoPP combined with losartan led to the restoration of their normal levels. ICP demonstrated significant decline in diabetic rats. The use of CoPP and/or losartan led to its significant improvement compared with diabetic rats. Administration of either losartan and/or CoPP led to a significant increase in the cavernous sinusoids surface area of diabetic rats. Administration of losartan with SnMP significantly decreased the enhancing effect of losartan on the studied parameters.ConclusionThe decline in erectile function in diabetes mellitus could be attributed to the downregulation of HO‐1 gene expression. HO‐1 induction added to Ang II receptor antagonist could improve erectile function. Abdel Aziz MT, El Asmer MF, Mostafa T, Atta H, Mahfouz S, Fouad H, Rashed L, Sabry D, Hassouna A, Abdel Aziz AT, Senbel A, and Demery A. Effects of losartan, HO‐1 inducers or HO‐1 inhibitors on erectile signaling in diabetic rats.     

Altered thyrotropic and lactotropic axes regulation in Huntington’s disease

Background Recently, a loss of hypothalamic dopamine D₂ receptors was demonstrated in Huntington’s disease (HD). Activation of dopamine D₂ receptors is known to inhibit the function of both thyrotropic and lactotropic axes. Objective To assess whether the activity of the thyrotropic and lactotropic axes is disturbed in patients with HD, contributing to symptoms such as unintended weight loss. Participants and methods In nine medication‐free patients with early‐stage HD (six men, three women) and nine age‐, sex‐ and body mass index‐matched controls, we measured serum levels of thyroid‐stimulating hormone (TSH) and prolactin (men only) every 10 min for 24 h. Multiparameter auto‐deconvolution and approximate entropy analysis were applied to quantify basal, pulsatile and total TSH and prolactin secretion rates as well as the regularity of hormone release. Results Compared with controls, TSH and prolactin secretion tended to be slightly, but not significantly, higher in patients with HD (TSH: 1·13 ±0·14 vs 0·91 ± 0·19 mU/l, P = 0·40; prolactin: 213 ± 18 vs 209 ± 11 pmol/l, P = 0·87). However, in patients with HD, total T₃ levels were significantly higher (1·60 ± 0·05 vs 1·35 ± 0·09, P = 0·045), while T₄ levels tended to be higher as well (91·9 ± 3·9 vs 81·3 ± 3·1, P = 0·085). Prolactin secretion was significantly more irregular in patients with HD (Approximate entropy (ApEn): 1·06 ± 0·08 vs 0·80 ± 0·09, P = 0·037). Total T₃ levels were negatively associated with motor impairment (r = ?0·72, P = 0·030), whereas increasing free T₄ levels were associated with a larger mutant cytosine‐adenine‐guanine (CAG) repeat size (r = +0·68, P = 0·044). Conclusion: Our findings indicate a mild hyperactivity of the thyrotropic axis and a disturbed regulation of the lactotropic axis in patients with early‐stage HD.     

Preparation and in vitro/pharmacokinetic/pharmacodynamic evaluation of a slow-release nano-liposomal form of prednisolone

A nano-liposomal carrier was prepared for the anti-inflammatory drug prednisolone acetate (PA). The drug showed remarkable loading in the nano-carriers. The drug-loaded nano-liposmes with average sizes of about 186?nm and zeta potentials of??20?mV were obtained. Our drug release studies showed an apparently zero-order trend with only 18% of the drug released in the first 120 h. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analyses showed no chemical interaction between the drug and carrier. Transmission electron microscopy (TEM) imaging showed near-spherical drug-containing nano-carriers. The intramuscular (IM) trial of the nanoformulation compared with the free drug showed both pharmacokinetic (lower C_max, higher area under the curve (AUC)) and pharmacodynamic (higher and longer lasting anti-inflammatory effect, both macroscopically and biochemically) superiority for the nano-liposomal drug above the free prednisolone in rats.     

Orbital lymphangioma and persistent fetal vasculature

A 12-year-old girl had an orbital lymphangioma and ipsilateral persistent hyperplastic primary vitreous (recently termed persistent fetal vasculature). Persistent fetal vasculature, orbital combined venous lymphatic vascular malformations, and noncontiguous intracranial vascular malformations may reflect the same defect in embryonal vascular maturation occurring in different tissues. Physicians caring for patients with orbital lymphangiomas should search for subtle signs of ipsilateral microphthalmos and should consider neuroimaging to evaluate for intracranial vascular malformations.     

Chorea associated with gabapentin use in an elderly man

Background: Chorea is a hyperkinetic movement disorder characterized by irregular, flowing, nonstereotyped, random, involuntary movements. Huntington disease (HD) and drug-induced chorea account for >50% of adult-onset cases. Chorea associated with gabapentin, an anticonvulsant, has not been well documented.Objective: The purpose of this article was to report a case of chorea that developed in an elderly man being treated with gabapentin for severe anxiety.Case summary: A 75-year-old white man (height, 165.1 cm; weight, 65.8 kg; body mass index, 19.6 kg/m2) with anxiety disorder not otherwise specified was admitted to a geriatric medicine psychiatric unit in Connecticut because of worsening symptoms of anxiety affecting his cognitive ability. On evaluation, the patient had choreiform movements involving the neck, trunk, upper and lower extremities, and tongue. The patient reported that symptoms began after taking gabapentin 300 mg PO TID (prescribed by his geriatrician) for the treatment of anxiety. The patient had been taking gabapentin for >1 month when the symptoms first appeared. There was no known family history of HD, and patient workup was unremarkable for other conditions (eg, vascular disease of the brain, progressive dementia, infectious and metabolic disorders) that might present with chorea. The chorea lasted for ~4 months and resolved within 2 days after gabapentin discontinuation.Conclusion: This article reports a case of chorea in an elderly patient who was receiving gabapentin for the treatment of anxiety. After gabapentin discontinuation, the chorea resolved completely, indicating a probable adverse drug reaction.     

Staghorn rhinolith in nasopharynx: an unusual case

The present case report is of a young female with complaint of foul smelling nasal discharge normal anterior rhinoscopic findings and an irregular mass on digital palpation of nasopharynx, confirmed by NCCT and extracted through oral route