Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling

IntroductionTraditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β₁-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism.AimWe evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues.MethodsErectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined.Main Outcome MeasuresThe effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses.ResultsTreatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals.ConclusionsNebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling.     

Asthma and contact urticaria caused by rice in a housewife

We report the case of an atopic housewife who presented with rhinoconjunctivitis-asthma and contact urticaria from handling rice and other cereals. She tolerated cooked cereals. Both skin prick tests with a rice extract (20% w/v) and a rub test with raw rice gave positive results. Bronchial challenge test with methacholine revealed a PC₂₀ of 0.45 mg/ml. The challenge test with raw rice resulted in immediate and late clinical and spirometric responses; pretreatment with DSCG inhibited both responses. The histamine release test (HRT) with rice was positive, and we detected rice-specific IgE antibodies by REIA in the patient's serum. Skin prick tests, HRT, and RAST with a battery of cereals gave positive results. Finally, the rice REIA was inhibited by rice (75%), rye (63%), corn (64%), and wheat (51%) extracts.     

Kaposiform lymphangiomatosis treated with multimodal therapy improves coagulopathy and reduces blood angiopoietin‐2 levels

Kaposiform lymphangiomatosis (KLA) is a rare, life‐threatening congenital lymphatic malformation. Diagnosis is often delayed due to complex indistinct symptoms. Blood angiopoietin‐2 (ANG2) levels are elevated in KLA and may be useful as a biomarker to monitor disease status. We report a 7‐year‐old male child with easy bruising, inguinal swelling, and consumptive coagulopathy, diagnosed with KLA. A multimodal treatment regimen of prednisone, sirolimus, vincristine, and adjunctive zoledronate was used. Plasma ANG2 levels were highly elevated at diagnosis but decreased during treatment. The patient showed significant clinical improvement over a 38‐month period and normalization of ANG2 levels correlated with resolution of the coagulopathy.     

Effects of human sera and human serum albumin on mouse embryo culture

Human proteins normally used to supplement human in vitro fertilization—embryo transfer (IVF-ET) culture media were tested for their effects on mouse embryo development from the zygote stage. These proteins included follicular and luteal-phase maternal sera, fetal cord sera, and both human and bovine serum albumin. Our results revealed that both maternal and fetal cord sera did not permit mouse blastocyst formation. Furthermore, predialysis of the human maternal sera and removal of IgG by protein A column chromatography did not improve their support of mouse embryonic development to the blastocyst stage. Similar detrimental effects were observed with maternal sera from term-pregnant IVF-ET patients. Interestingly, these serum samples had supported the in vitro growth of the human zygotes which resulted in these patients' pregnancies. Only some batches of human serum albumin supported mouse blastocyst formation, whereas all sources of bovine serum albumin were effective in this regard. These results raise the question of the suitability of the mouse embryo culture system as a quality control for the testing of protein supplements for human IVF-ET.     

Relationship of insulin resistance and overweight with cortisol and dehydroepiandrosterone-sulfate levels

BACKGROUND: Our objective was to assess the relationship of hormones such as cortisol and dehydroepiandrosterone-sulfate (DHEA-S) with insulin resistance and overweight. METHODS: We designed and conducted a cross-sectional, observational survey consisting of home visits within a previously defined area of Mexico City. The study included 303 apparently healthy volunteers from a middle-class socioeconomic urban community. We measured glucose, cholesterol, triglycerides, insulin, cortisol, and DHEA-S. Insulin resistance (IR) was defined as belonging to the first quartile of fasting glucose/insulin ratio (G/IR) distribution or fourth quartile of IR (HOMA). Overweight was defined as body mass index (BMI) > or =25 kg/m(2). RESULTS: To predict IR in women < or =35 years of age, principal component analysis (PCA) disclosed three components: 1) cholesterol, BMI, and diastolic blood pressure (DBP); 2) cholesterol, triglycerides, and cortisol, and 3) dehydroepiandrosterone-sulfate [DHEA-S]. Solely the latter (DHEA-S) was significantly associated with IR (odds ratio [OR] = 1.80, confidence interval 95% [CI 95%] 1.11-2.91, p = 0.015). For men < or =35 years of age, there were two components: 1) cholesterol, triglycerides, BMI, and DBP, and 2) DHEA-S, cholesterol, and cortisol. Component 1 was significantly associated with IR (OR = 5.65; CI 95% 1.62-19.65, p = 0.006). To predict overweight in women >35 years of age, there were three components, including 1) cholesterol and triglycerides, 2) cortisol, and 3) DHEA-S and G/IR. Component 2 was significantly associated with overweight (OR = 0.38, CI 95% 0.23-0.64, p = 0.000). CONCLUSIONS: In women < or =35 years of age, high DHEA-S levels were associated with insulin resistance, which suggests that in young women DHEA-S exerts anti-estrogenic action, perhaps caused by its competitive binding with the estrogen receptor. Additionally, in women >35 years of age, low cortisol levels were associated with overweight. These associations were not identified for the male subgroup.     

Cell-specific effects of RB or RB/p107 loss on retinal development implicate an intrinsically death-resistant cell-of-origin in retinoblastoma

Retinogenesis involves expansion of pluripotent progenitors, specification of postmitotic precursors, and terminal differentiation. Rb or Rb/p107 loss causes retinoblastoma in humans or mice, respectively. One model suggests that Rb- or Rb/p107-deficient retinal precursors have infinite proliferative capacity but are death-prone and must acquire an antiapoptotic mutation. Indeed, we show that Rb/p107 loss does not affect progenitor proliferation or precursor specification, but perturbs cell cycle exit in all seven retinal precursors. However, three precursors survive Rb/p107-loss and stop proliferating following terminal differentiation. Tumors arise from precursors that escape this delayed growth arrest. Thus, retinoblastoma arises from a precursor that has extended, not infinite, proliferative capacity, and is intrinsically death-resistant, not death-prone. We suggest that additional lesions common in retinoblastoma overcome growth arrest, not apoptosis.     

Information technology in health professional education: why IT matters

This paper analyses the potential of information technology (IT) to transform the process of learning in higher education, particularly health professional education. It is argued that IT, although very much part of the infrastructure of the modern university has yet to make its full impact on teaching and learning processes. The expectations of students and demands for improved flexibility and access make it inevitable that IT will become an integral part of teaching and learning despite inherent resistance to change. The potential benefits of IT are identified as: transmission of high quality content, support of life-long learning, flexibility of access and enhanced opportunities for communication. These concepts are explored in the context of health professional education. It is argued that universities cannot survive without harnessing the power of IT to improve the educational experience of students but lecturers should ensure that this is underpinned by sound educational theory.     

Assessment and treatment of chest pain

Chest pain is one of the main reasons for emergency admission to hospital in the UK. Jackie Tough examines the causes and treatment of chest pain and offers a structured system for taking the patient's history.