A Review of the Therapeutic Targeting of SCN9A and Nav1.7 for Pain Relief in Current Human Clinical Trials.

Introduction: There is a great need to find alternative treatments for chronic pain which have become a healthcare problem. We discuss current therapeutic targeting Nav1.7. Areas Covered: Nav1.7 is a sodium ion channel protein that is associated with several human pain genetic syndromes. It has been found that mutations associated with Nav1.7 lead to the loss of the ability to perceive pain in individuals that are otherwise normal. Several therapeutic interventions are presently undergoing preclinical and research using the methodology of damping Nav1.7 expressions as a methodology to decrease the sensation of pain leading to analgesia. Expert Opinion: It is our strong belief that there is a viable future in the targeting of protein of Nav1.7 for the relief of chronic pain in humans. The review will look at the genomics associated with SCN1A and proteomic of Nav1.7 as a foundation to explain the mechanism of the therapeutic interventions targeting Nav1.7, the human disease that are associated with Nav1.7, and the current development of treatment for chronic pain whether in preclinical or clinical trials targeting Nav1.7 expressions. The development of therapeutic antagonists targeting Nav1.7 could be a viable alternative to the current treatments which have led to the opioid crisis. Therefore, Nav1.7 targeted treatment has a major clinical significance that will have positive consequences as it relates to chronic pain interventions.

Compatibility of Isaria fumosorosea (Hypocreales: Cordycipitaceae) Blastospores with Agricultural Chemicals Used for Management of the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Liviidae).

Biorational insecticides are being increasingly emphasized for inclusion in integrated pest management programs for invasive insects. The entomopathogenic fungus, Isaria fumosorosea, can be used to help manage the Asian citrus psyllid with minimal impact on beneficial arthropods, but its effectiveness may be compromised by agrochemicals used to control concurrent arthropod pests and diseases. We evaluated the compatibility of I. fumosorosea blastospores with a range of spray oils and copper-based fungicides registered for use in citrus groves. Results of laboratory and greenhouse tests showed a range of responses of the fungus to the different materials, including compatibility and incompatibility. Overall, I. fumosorosea growth in vitro was reduced least by petroleum-based materials and most by botanical oils and borax, and some of the copper-based fungicides, suggesting that tank mixing of I. fumosorosea with these latter products should be avoided. However, equivalent negative effects of test materials on fungal pathogenicity were not always observed in tests with adult psyllids. We hypothesize that some oils enhanced adherence of blastospores to the insect cuticle, overcoming negative impacts on germination. Our data show that care should be taken in selecting appropriate agrochemicals for tank-mixing with commercial formulations of entomopathogenic fungi for management of citrus pests. The prospects of using I. fumosorosea for managing the invasive Asian citrus psyllid and other citrus pests are discussed.

Puberty: timing is everything.

When evaluating delayed puberty, it is essential to determine the underlying cause. This can be done with history and physical exam as well as basal gonadotropin levels, bone age, and further testing as indicated. When the cause is hypogonadism, an underlying condition should be treated if present; otherwise lifelong hormonal therapy is necessary. When constitutional delay is present, each case must be handled individually. Most patients can be reassured while some may require transient hormonal treatment for psychosocial reasons. Patients receiving hormonal therapy may require assistance from an endocrinologist and close monitoring.

The multiple indications for growth hormone treatment of pediatric patients.

GH has many approved uses in pediatric patients including GH deficiency, CRF, Turner syndrome, Prader-Willi syndrome, SGA, and ISS. The child should have an appropriate evaluation for poor growth and endocrine consultation as dictated by clinical and investigative findings. Treatment of the child with GH deficiency is universally accepted. Treatment of children with Turner syndrome is dependent on the child's growth and stature with early diagnosis and treatment offering the most favorable outcome. Prescription of GH for PWS patients should be done cautiously given the possible association between GH use and sudden death; further studies are needed to fully delineate such a relationship. If a child has a history of SGA and is below the 3rd percentile at age 2, endocrine referral should be considered. Adult heights within the normal range may be attained in SGA patients treated with GH. An individualized approach to children with ISS should be practiced. The clinician should take into consideration factors such as psychosocial concerns and must exclude alternative etiologies of poor growth prior to consideration of therapy with GH. For all etiologies, greater height gains generally have been shown to be associated with younger age at time of diagnosis and treatment. There are ethical, economic and psychosocial issues surrounding GH use in children such that sound clinical practice should include an individualized approach to any patient who may be a potential candidate for GH treatment.

Open-label trial of an injection depot formulation of buprenorphine in opioid detoxification.

Buprenorphine, a partial mu-opioid agonist, has been shown effective for treatment of opioid dependence but also has some abuse potential. A novel formulation of buprenorphine, using a polymer microcapsule depot sustained-release technology, has been developed which may offer effective treatment of opioid dependence while also minimizing risks of patient noncompliance and illicit diversion. This open-label, first-in-human study evaluated the safety and pharmacokinetics of a single-dose buprenorphine depot in physically dependent opioid abusers. The present study also examined the efficacy of depot buprenorphine in suppressing symptoms of opioid withdrawal, attenuating the effects of exogenous opioid challenge, and providing clinical detoxification. Five opioid-dependent volunteers each received a single subcutaneous depot injection containing 58 mg of buprenorphine and were assessed for at least four weeks for signs and symptoms of opioid withdrawal, first residentially and then as outpatients. Depot buprenorphine appeared to provide effective relief from opioid withdrawal, with no participant requiring additional medication for withdrawal relief following depot administration. The depot was safe and well-tolerated, with no significant side effects, signs of intoxication, or respiratory depression. In the opioid challenge sessions, depot buprenorphine appeared to produce substantial opioid blockade that persisted for 6 weeks post-depot administration. Results from the present study suggest that depot buprenorphine offers significant promise for enhancing the delivery of effective opioid agonist treatment while minimizing risk for abuse of the medication.

Type 2 diabetes mellitus in youth.

In the United States, the incidence of type 2 diabetes mellitus (DM) in children and adolescents has been increasing at an alarming rate. Early recognition and intervention can delay the onset of type 2 DM and prevent the long-term complications. School nurses have an essential role in implementing the American Diabetes Association (ADA) recommended screening guidelines to identify youth at high risk for type 2 DM and in implementing student health programs that focus positively on the importance of physical activity and healthy eating habits. The purpose of this article is to present an overview of the epidemiology, pathophysiology, complications, diagnosis, and treatment, as well as the recommended screening guidelines for type 2 DM in the pediatric age group. The information provided will enhance awareness, promote screening, and empower the school nurse to more effectively promote healthy lifestyle education.

Depot naltrexone: long-lasting antagonism of the effects of heroin in humans.

RATIONALE: Naltrexone, an opioid antagonist, is currently approved as a treatment for heroin dependence. However, naltrexone is generally not well accepted by patients, and medication non-compliance is a difficult obstacle to treatment. A sustained-release form of naltrexone may improve compliance. OBJECTIVE: The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex). METHODS: Twelve heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, six participants received 192 mg naltrexone base and six participants received 384 mg naltrexone base. For safety, the low dose of depot naltrexone was tested before the high dose. The effects of heroin (0, 6.25, 12.5, 18.75, 25 mg, i.v.) were evaluated for the next 6 weeks. One dose of heroin was tested per day on Mondays through Fridays, and the entire dose range was tested each week. Active heroin doses were administered in ascending order during the week, while placebo could be administered on any day. Subjective, performance, and physiological effects were measured both before and after heroin administration. The hypotheses were that depot naltrexone would antagonize the effects of heroin, and that the high dose of depot naltrexone would produce a more effective and longer-lasting antagonism than the low dose. RESULTS: The low and high doses of depot naltrexone antagonized heroin-induced subjective ratings for 3 and 5 weeks, respectively. Plasma levels of naltrexone remained above 1 ng/ml for approximately 3 and 4 weeks after administration of 192 mg and 384 mg naltrexone. Other than the initial discomfort associated with the injection of depot naltrexone, there were no untoward side-effects. CONCLUSIONS: These results suggest that this depot formulation of naltrexone provides a safe, effective, long-lasting antagonism of the effects of heroin.

Type 2 diabetes mellitus in adolescents.

While diabetes mellitus types 1 and 2 used to be distinguished largely by age at onset, in the past decade there has been an increase in the number of children presenting with diabetes that can be controlled with oral medications. This has lead to these children being diagnosed with type 2 diabetes mellitus despite their young age. This chapter offers an overview of presenting features, pathophysiology, treatment and prognosis of this disorder in the adolescent patient. Additionally, it offers information regarding the relationship between increasing childhood obesity and a rise in the reported cases of diabetes in children. Appropriate screening and laboratory tests and their results are explained, and the pros and cons of both pharmacologic and non-pharmacologic therapies are discussed. Some complications of diabetes in the developing adolescent differ from those adults will face, and the well-known complications of diabetes (hyperlipidemia, hypertension) must be addressed in a population that is not normally screened for these health concerns. It is hoped that by educating physicians to the potential for this disorder in their adolescent patients, long-term complications can be reduced and advanced sequelae of vascular and neurologic problems can possibly be avoided altogether.