Safety and Efficacy of Human Chorionic Gonadotropin (hCG) in Weight Loss

Human Chorionic Gonadotropin (hCG) has recently experienced a resurgence in popular media. Late night television commercials and Internet advertisements have suggested that it is an essential, unequivocal means to losing weight fast. ls hCG really a miracle cure to help patients shed unwanted pounds? In 1954, A.T.W. Simeons claimed that hCG impacts weight loss by decreasing hunger, increasing fat redistribution, and increasing overall mood. Knowing that weight loss cannot be directly attributed to hCG use, Simeons developed a very low calorie diet (VLCD) to which the success of the therapy can be attributed. He saw hCG as a means to an end. Following a VLCD is nearly impossible without a little push, and according to Simeons, this push could be hCG. This increase in mood is an essential reagent to following a low calorie, thus low-energy diet, and therefore is necessary for the product of weight loss. Combination therapy of hCG and diet has been studied using multiple dosage forms, but no definitive answer has been found

An Update on Gestational Diabetes

Gestational diabetes is a concern for a large number of pregnant women due to the potential for long-term complications for both the mother and the fetus. With the increasing prevalence of obesity and diabetes in the general public, the number of pregnant women with undiagnosed type 2 diabetes mellitus has also increased. In order to adequately educate their patients, it is important for pharmacists to be aware of the general practices of treating gestational diabetes. This review will highlight recent updates to initial screening, the criteria for diagnosing gestational diabetes, and current management strategies

α1D-Adrenoceptors are responsible for the high sensitivity and the slow time-course of noradrenaline-mediated contraction in conductance arteries

The objective of this study was to determine whether the different time-course characteristics of α1-adrenoceptor-mediated contraction in arteries can be related to the subtypes involved. Contractile responses to noradrenaline (NA) were compared with inositol phosphate accumulation and extracellular signal-regulated kinase (ERK)1/2 phosphorylation after α1-agonist stimuli in the same vessels in the presence or absence of α1-antagonists in rat or in α1-subtype knockout (KO) mice. Aorta, where α1D-AR is the main functional subtype, had higher sensitivity to NA (in respect of inositol phosphate [IP], pERK1/2, and contractile response) than tail artery, where the α1A-adrenoceptor subtype is predominant. Furthermore, the contraction in aorta exhibited a slower decay after agonist removal and this was consistent in all strains harboring α1D-adrenoceptors (from rat, α1B-KO, and wild-type [WT] mice) but was not observed in the absence of the α1D-adrenoceptor signal (α1D-adrenoceptor blocked rat aorta or aorta from α1D-KO). IP formation paralleled α1-adrenoceptor-mediated contraction (agonist present or postagonist) in aorta and tail artery. High sensitivity to agonist and persistence of response after agonist removal is a property of α1D-adrenoceptors. Therefore, the preponderance of this subtype in noninnervated conductance arteries such as aorta allows responsiveness to circulating catecholamines and prevents abrupt changes in vessel caliber when the stimulus fluctuates. Conversely, in innervated distributing arteries, high local concentrations of NA are required to activate α1A-adrenoceptors for a response that is rapid but short lived allowing fine adjustment of the contractile tone by perivascular sympathetic nerves

Immunocytochemical localization of the alpha-1B adrenergic receptor and the contribution of this and the other subtypes to vascular smooth muscle contraction: analysis with selective ligands and antisense

ABSTRACT The contribution of the alpha-1B adrenergic receptor (AR) to vascular smooth muscle contraction has been assessed using a combination of immunological, molecular biological and pharmacological approaches. A subtype-selective antibody detected alpha-1B immunoreactivity in the medial layer of the aorta, caudal, femoral, iliac, mesenteric resistance, renal and superior mesenteric arteries. Receptor protection assays and antisense oligonucleotides were used to assess the contribution of the alpha-1B AR to contraction. The alpha-1B AR was implicated in mediating the phenylephrine-induced contraction of the mesenteric resistance artery. The alpha-1D AR was implicated in mediating the contraction of the aorta, femoral, iliac and superior mesenteric arteries. Similarly, the alpha-1A AR was implicated in mediating contraction of the caudal and renal arteries. In vivo application of antisense oligonucleotides targeted to the translational start site of the alpha-1B AR had no effect on the phenylephrine-induced contraction of the femoral or renal arteries. In contrast, antisense oligonucleotides directed against the alpha-1D AR significantly inhibited the phenylephrine response in the femoral artery but had no effect on the renal artery. Application of alpha-1A AR antisense oligonucleotides inhibited the contraction of the renal artery without effect on the femoral artery. These data show that (1) alpha-1B AR immunoreactivity is widely distributed in the same peripheral arteries in which previous studies detected its mRNA, and (2) despite this distribution, receptor protection and antisense oligonucleotide studies indicate that the alpha-1B AR mediates the contraction of only the mesenteric resistance artery. The alpha-1 AR family is a member of the G proteincoupled superfamily of receptors. In analogy to bacteriorhodopsin, these receptors have the now very familiar proposed structure of seven transmembrane spanning domains connected by hydrophilic loops alternately exposed to the extracellular and intracellular environment. The structure of G protein-coupled receptors in general and alpha-1 ARs specifically have been the subject of several reviews (Bylund et a

Expression and function of G-protein-coupled receptorsin the male reproductive tract

This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.Esta revisão enfatiza a expressão e a função dos receptores muscarínicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressão dos receptores muscarínicos e adrenoceptores α1 em compartimentos específicos de dúctulos eferentes, epidídimo, ductos deferentes, vesícula seminal e próstata de várias espécies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do músculo liso, incluindo efeitos na fertilidade masculina. Além disso, a ativação dos receptores muscarínicos leva à transativação do receptor para o fator crescimento epidermal e proliferação das células de Sertoli. Os receptores para relaxina estão presentes no testículo, RXFP1 nas espermátides alongadas e células de Sertoli de rato e RXFP2 nas células de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogênico. A localização de ambos os receptores na porção apical das células epiteliais e no músculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

Sildenafil in the treatment of pulmonary hypertension

Pulmonary arterial hypertension is a progressive disease that has a high rate of mortality. For these reasons, early treatment is essential. Treatment choices for pulmonary arterial hypertension are limited by drug tolerability, drug cost and inconvenience associated with administration techniques and dosing schedules. Therefore, a therapy that provides oral dosing with limited side effects would prove useful in managing many patients. Sildenafil citrate, the first and highly publicized oral medication to receive approval from the U.S. Food and Drug Administration for erectile dysfunction, has recently been approved for treatment of pulmonary arterial hypertension. This review summarizes the normal physiology of the pulmonary vasculature, and the pathophysiology involved in pulmonary arterial hypertension and the role of sildenafil in its treatment

Role of ambrisentan in pulmonary hypertension

OBJECTIVE: To review the role of ambrisentan in the treatment of pulmonary arterial hypertension (PAH). DATA SOURCES: Literature was accessed through MEDLINE (1950-June 2008), Iowa Drug Information Service (1966-March 2008), EMBASE (1966-June 2008), bibliographies of pertinent articles, and unpublished data provided by the manufacturer and the Food and Drug Administration (FDA). Search terms included ambrisentan, endothelin antagonist, pulmonary hypertension, and pulmonary arterial hypertension. Due to limited literature available, additional criteria to limit searches were not used. STUDY SELECTION AND DATA EXTRACTION: Abstracts and original preclinical and clinical research reports available in the English language were identified for review. All manufacturer-provided data were also evaluated. Literature related to ambrisentan, endothelin antagonists, pulmonary hypertension, and pulmonary arterial hypertension were included. Four clinical trials evaluated the efficacy of ambrisentan in adults with symptomatic PAH. DATA SYNTHESIS: Ambrisentan is the latest endothelin-receptor antagonist (ERA) to obtain FDA approval for the treatment of PAH. It joins the first FDA-approved ERA, bosentan. Like bosentan, ambrisentan is available orally (with once-daily dosing compared with bosentan\u27s twice-daily dosing) and has been shown to improve exercise capacity and delay clinical worsening. As with bosentan, the most significant safety concerns with ambrisentan relate to potential liver injury and a contraindication in pregnancy. Although ambrisentan has higher affinity for the endothelin type A receptor than for the endothelin type B receptor, specific advantages of this selectivity, in terms of efficacy compared with bosentan, a nonselective agent, have not been demonstrated. CONCLUSIONS: Ambrisentan has been shown to be an effective ERA in patients with PAH. A significant advantage of ambrisentan is the lack of any clinically important drug interactions with warfarin and sildenafil, which are frequently used by patients being treated for PAH

Use of sildenafil for female sexual dysfunction

OBJECTIVE: To review the pathophysiology of female sexual dysfunction (FSD) and the literature regarding the use of sildenafil in its treatment. DATA SOURCES: Literature was accessed through MEDLINE (1966-April 2006), Iowa Drug Information Service (1966-April 2006), EMBASE (1966-April 2006), and bibliographies of pertinent articles. Search terms included female sexual dysfunction; sexual dysfunction, psychological; phosphodiesterase inhibitors; and sildenafil. DATA SYNTHESIS: The lack of a clear understanding of FSD contributes to the limited treatment options available. Studies regarding the safety and efficacy of the phosphodiesterase 5 inhibitor sildenafil in the management of FSD were evaluated. Many trials have been of poor quality, making clinical application of their results difficult. The current literature does not show sildenafil to be an effective treatment option for FSD. CONCLUSIONS: Treatment of FSD should include both physical and psychological components. Based on the limited data available, it appears that sildenafil, while well tolerated, offers little or no benefit to most patients with FSD

Answers About the Need for Vitamin D Supplementation

Vitamin D has a significant role in bone health, calcium homeostasis, immune function and other biological functions. In our bodies, the main source of vitamin D is linked to our skin\u27s exposure to sunlight. It can also be obtained through foods that contain vitamin D. Despite these two sources, vitamin D supplementation is often necessary. It is available in two forms, cholecalciferol and ergocalciferol as over-the-counter (OTC) products, as well as calcitriol as prescription only. Reasons for vitamin D deficiency include lack of sunlight, poor diet, malabsorption of vitamin D, liver and/or kidney disease. Vitamin D deficiencies lead to diseases such as rickets, osteomalacia and osteoporosis. During supplementation it is important to monitor for vitamin D toxicity. Pharmacists need to be aware of the various guidelines regarding vitamin D supplementation