Flow injection potentiometric determination of amantadine HCl

New amantadine (Am) ion selective plastic membrane electrodes of both conventional and coated graphite types based on the ion-pair of amantadinium tetraphenylborate (Am-TPB) ion-pair are prepared. The conventional type electrode was fully characterized in terms of membrane composition, life span, pH, ionic strength and temperature. It was applied to potentiometric determination of amantadine in pure state and pharmaceutical preparation under batch and flow injection conditions. The selectivity of the electrode toward a large number of inorganic cations, sugars and amino acids was tested. The solubility product of the ion-pair and the formation constant of the precipitation reaction leading to the ion-pair formation were determined conductimetrically.     

Nutritional status of Palestinian preschoolers in the Gaza Strip: a cross-sectional study

Background  

The authors examined factors associated with nutritional resilience/vulnerability among preschoolers in the Gaza Strip in 2007, where political violence and deprivation are widespread.     

Assessing Community-Based Injury Prevention Services in U.S. Children's Hospitals

ObjectiveNot-for-profit hospitals are required to meet federal reporting requirements detailing their community benefit activities, which support their tax-exempt status. Children''s hospitals have long provided community injury prevention (IP) programming and thus can inform public health outreach work in other areas. This work describes IP programming as a community service offered by children''s hospitals in the U.S.MethodsThe IP specialist at 232 US-based member institutions of the Children''s Hospital Association were invited to complete an assessment of their hospital''s IP outreach programming.Results47.7 percent of hospitals request financial data from IP programming for tax reporting purposes. Almost all offer injury prevention (IP) services; the majority are in the community (60.3%) and 34.5% are hospital-based. Most IP units are independent (60.3%) and 71.8% are responsible for their own budgets.ConclusionsBy integrating dissemination and implementation sciences and community health needs assessments, these findings can help advance community services provided by hospitals to impact public health.     

Is miR‐34a a Well‐equipped Swordsman to Conquer Temple of Molecular Oncology?

Overwhelmingly increasing advancements in miRNA biology have opened new avenues for pharmaceutical companies to initiate studies on designing effective, safe, and therapeutically active candidates using miRNA mimetics and miRNA inhibitors. In accordance with this approach, development of miravirsen and SPC3649, an LNA‐based (locked nucleic acid) antisense molecule against miR‐122, to treat hepatitis C has sparked interest in identifying most efficient microRNAs for journey from bench‐top toward pharmaceutical industry and breakthroughs in delivery technology will pave the way to ‘final frontier’. MRX34, a liposome‐formulated mimic of miR‐34 for treatment of metastatic cancer with liver involvement and unresectable primary liver cancer, has also entered in clinical trial. There is a successive increase in the research work related to miR‐34 biology and miRNA regulation of modulators of intracellular signaling cascades. We partition this review into how miR‐34a is regulated by different proteins and how Wnt‐ and TGF‐induced intracellular signaling cascades are modulated by miR‐34a. In this review, we bring to limelight how miR‐34a regulates its target genes to induce apoptosis and inhibit cell proliferation as evidenced by in vitro and in vivo analysis. We also discuss miR‐34 regulation of PDGFR and c‐MET and recent advancements in nanotechnologically delivered miR‐34a. Spotlight is also set on modulation of chemotherapeutic sensitivity by miR‐34a in cancer cells using reconstruction studies. Clinical trial of miR‐34 is indicative of its tremendous potential, and continuous cutting research will prove to be effective in efficiently translating laboratory findings into clinically effective therapeutics.     

Dietary fish oil increases lipid mobilization but does not decrease lipid storage-related enzyme activities in adipose tissue of insulin-resistant,sucrose-fed rats

Fish oil feeding has been shown to limit visceral fat accumulation in insulin-resistant rats. Our goal was to determine whether this finding is due to increased fat mobilization or decreased lipid storage. Adipocytes were isolated from rats fed for 3 wk a diet containing 57.5 g/100 g sucrose and 14 g/100 g lipids as either fish oil (SF) or a mixture of standard oils (SC); there was also a reference group (R). Substituting fish oil for standard oils protected rats from visceral fat hypertrophy, hypertriglyceridemia and hyperglycemia. The stimulation of lipolysis was greater in adipocytes isolated from SF-fed rats than in those from SC-fed rats. Fatty acid synthase (FAS) activity was markedly lower in the liver but not in the adipose tissues of rats fed SF. Lipoprotein lipase (LPL) activity was 2.2-fold higher in the adipose tissues but not in the muscle in rats fed the SF diet than in those fed the SC diet. The decrease in visceral fat in rats fed fish oil could be attributed to decreased plasma triacylglycerol concentration and/or increased lipid mobilization rather than to reduced lipid storage.     

A healthy infant with bloody tears: Case report and mini-review of the literature

A 4-month old healthy infant was brought by her parents to the emergency department with bloody tears of three days duration. There was also intermittent yellowish discharge since birth and a history of flu-like symptoms a week prior to presentation. Extensive investigations revealed no infection or other possible etiologies. The patient was treated with antibiotic eye drops and her condition resolved within a three-four days.In the literature, 15 cases with haemolacria of undermined source were reviewed; the median age of onset (12?years), bilateral involvement and female gender were more commonly encountered, and the most common associated illnesses were headache and epistaxis. The condition is self-limiting and spontaneous resolution is seen in majority of cases. Idiopathic haemolacria is a rare condition that can be presumed in patients presenting with bloody tears when all work-up turns to be negative. The condition is self-limiting with spontaneous resolution.     

CEA-related proteins on human urothelial cell lines of different transformation grades.

CEA family proteins from human urothelial cell lines of different transformation grades were characterized by flow cytometry and Western blotting using monoclonal antibodies: 26/3/13, D14HD11, 9A6 and 4/3/17. The following observations were made: (i) the urothelial cell lines, representing transformation grade III (TGr III, tumorigenic, invasive cells), were characterized by the presence of a component with molecular mass 110-135 kDa, most probably representing biliary glycoprotein (BGP); (ii) BGP was absent in non-tumorigenic and non-invasive TGr II urothelial cell lines; (iii) a protein band with apparent molecular mass 180 kDa, and migrating as a CEA standard was detected in only one of seven urothelial cell lines analyzed; (iv) a broad band of apparent molecular mass migrating at 65-90 kDa, probably representing NCA-50/90, was found in two tumorigenic and invasive cell lines, HCV 29T and Hu 1703He.     

Sonographic diagnosis of the entrapment of the flexor digitorum profundus tendon complicating a fracture of the index finger

Flexor digitorum tendon entrapment is a known complication of proximal phalangeal fractures and is commonly diagnosed clinically. However, it can sometimes be subtle and may not be suspected initially. A case of proximal phalangeal fracture of the index finger complicated by entrapment of the flexor digitorum profundus tendon is presented in which the diagnosis was made based on sonographic findings subsequently confirmed by CT and later surgical findings. This case demonstrates that tendon entrapment complicating phalangeal fractures can be diagnosed using sonography.     

Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees

OBJECTIVE— Melanocortin-4 receptor (MC4R) deficiency is the most frequent genetic cause of obesity. However, there is uncertainty regarding the degree of penetrance of this condition, and the putative impact of the environment on the development of obesity in MC4R mutation carriers is unknown.RESEARCH DESIGN AND METHODS— We determined the MC4R sequence in 2,257 obese individuals and 2,677 nonobese control subjects of European origin and established the likely functional impact of all variants detected. We then included relatives of probands carriers and studied 25 pedigrees, including 97 carriers and 94 noncarriers from three generations.RESULTS— Of the MC4R nonsynonymous mutations found in obese subjects, 68% resulted in a loss of function in vitro. They were found in 1.72% of obese versus 0.15% of nonobesed subjects (P = 6.9 × 10⁻¹⁰). Among the families, abnormal eating behavior was more frequent in both MC4R-deficient children and adults than in noncarriers. Although BMI was inversely associated with educational status in noncarrier adults, no such relationship was seen in MC4R mutation carriers. We observed a generational effect, with a penetrance of 40% in MC4R-deficient adults aged >52 years, 60% in 18- to 52-year-old adults, and 79% in children. The longitudinal study of adult carriers showed an increasing age-dependent penetrance (37% at 20 years versus 60% at >40 years).CONCLUSIONS— We have established a robust estimate of age-related penetrance for MC4R deficiency and demonstrated a generational effect on penetrance, which may relate to the development of an “obesogenic” environment. It remains to be seen whether appropriate manipulation of environmental factors may contribute to preventing the development of obesity even in those strongly genetically predisposed to it.The leptin-melanocortin axis controls human energy homeostasis, and the melanocortin-4 receptor (MC4R) is a key player in its central regulation (1). Loss-of-function mutations in MC4R cause severe familial forms of obesity (2,3), and infrequent gain-of-function polymorphisms have been associated with protection against obesity (4,5). At least 72 nonsynonymous mutations have been discovered so far, but some have no obvious functional consequences (6,7), highlighting the importance of functional characterization of MC4R mutations in the determination of potential pathogenicity. MC4R is a membrane-bound G-protein–coupled receptor that activates adenylate cyclase. Loss-of-function mutations result in a partial or complete loss of function as measured by cAMP production. The majority of missense mutations in MC4R result in intracellular retention of the mutated protein, whereas some primarily affect ligand binding or ligand/receptor activation (8,9). In some cases, the alteration of the basal activity of the receptor (8,10) has been reported.The prevalence of loss-of-function MC4R mutations ranges from 0.5 to 5.8% in childhood-onset obesity (11–14). The contribution of MC4R mutations to late-onset obesity is still debated (13,15–18). Obesity due to MC4R mutations has been extensively studied, and although heterozygous loss-of-function mutations can clearly cause familial obesity, they can be found in individuals who are not obese (19). There is a need for reliable estimates of penetrance. Furthermore, no study has thoroughly assessed the effect of loss-of-function MC4R mutations in elderly subjects. Previous studies using part of our French cohort evidenced the first mutation in MC4R and demonstrated that most of them lead to an intracellular retention of the receptor (2,13,18).Although hyperphagia is a key feature of MC4R deficiency, with increased food intake at an ad libitum test meal reported in severely obese MC4R-deficient children (10), an apparent amelioration of obesity and food intake disturbances has been suggested in adulthood in some studies (6,11). Obesity is a complex trait, and MC4R mutations offer a unique opportunity to analyze the effects of both aging and shared environment on the evolution of body mass in this paradigm. In this extensive study of 2,257 unrelated obese subjects, 2,677 control subjects of European descent, and 25 multigenerational pedigrees with several MC4R mutations carriers, we provide a comprehensive picture of the prevalence of this condition and of factors that determine the expression of the obesity phenotype and support previous observations reported in a German familial study (20).