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H. Umbrak, M.B.A., M.B.B.S., M.H.S.
Vice Chair, University of California, Davis School of Medicine
Many other murine models of the MetS have resulted from modifications of single genes. Although some of these models have been summarized in a previous review on the MetS (268), it is our intent in this review to provide an extensive list of the murine models of the MetS and characterize each of the models over the period of phenotypic development. Models with all three components are listed in Table 7 first (269 273), followed by those with two (227, 274 297), and finally those with only insulin resistance (298 311). The final mouse grouping is animals with a polygenic background that meet the criteria for the MetS as stated (312319). Details for each of the models including murine strain, gender, age, environmental exposure including diet, and components of the MetS phenotype plus related structural and/or functional abnormalities when present are all provided. Subsequently, a number of studies have been published to examine the impact of diet on the phenotypic development of the MetS (321326). In these rats, lymphatic chylomicron apoB48, chylomicron size, fasting and postprandial plasma apo B48 area under the curve are all elevated (334). Although these rats are not obese, they are hypertensive, insulin resistant, and glucose intolerant (335, 336). These rats also have obesity, dyslipidemia, and an increased insulin/glucose ratio. This rat strain has been used to identify linkage of body weight, blood pressure, and renal, metabolic, and endocrine phenotypes (338). This is a renindependent model of hypertension in which low-dose (nonantihypertensive) angiotensin-converting-enzyme inhibitor therapy affords significant and durable renal protection. Of interest to pet owners and veterinarians alike is the fact that obesity in dogs and cats has increased in recent years (343), and dogs in particular are models of the MetS. The canine obesity model closely recapitulates the relationship between human visceral adiposity and insulin resistance. The prevalence of diabetes has increased concomitantly with the increase in obesity, and diabetes is now seen in approximately 0. Cats develop a form of diabetes that is similar to T2D in humans, characterized by islet amyloid accumulation and loss of -cell mass (345). From more recent studies in felines, it appears that glucose metabolism in cats is similar to that in humans; however, lipid metabolism is quite different (346). This may explain why the MetS in cats is less frequent than in dogs and is not frequently studied. Hyperglycemia and impaired glucose clearance are also commonly associated with hyperlipidemia in primates (347). The prevalence and heritability of obesity and risk factors associated with the MetS in a pedigreed colony of Vervet monkeys has been reported recently (348). Vervet monkeys demonstrated obesity, insulin resistance, and associated changes in plasma lipids even while consuming a low-fat (chow) diet. In monkeys that develop diabetes, significant decreases in glucose tolerance were evident by middle age (age, 14 yr), with elevations in fasting insulin and then a progressive decline in insulin secretion with aging (349). With aging, rhesus monkeys with diabetes also demonstrated dyslipidemia and shifts in lipoprotein particle size and number as measured by nuclear magnetic resonance (350). In humans, Bjorntorp and Rosmond (351) were among the first to suggest that the MetS was caused by stress. Genetic determinants of the metabolic syndrome in humans Increasing evidence suggests that there is genetic basis for the MetS. As with most complex traits, however, the associations are quite weak, and the replication of findings has been poor. Some recently published reviews have summarized the results from multiple genome-wide scans involving different cohorts (353355). From these studies, familial aggregation is most evident for the individual components of the MetS; however, some studies suggest that specific genes, such as those that encode for 11 -hydroxysteroid dehydrogenase, adiponectin, and the 3-adrenergic receptor, may also predispose to the development of the MetS (356 358). Furthermore, it has been suggested that the risk of the MetS may be modified by dietary fatty acid composition (359). Of the five subphenotypes defining MetS, all are known to have strong genetic components (typically 50 80% of population variation).
Narcotics/opioids are controlled substances that vary from Schedule I to Schedule V, depending on their medical usefulness, abuse potential, safety, and drug dependence profile. Fentanyl is a potent synthetic opioid drug approved by the Food and Drug Administration for use as an analgesic (pain relief) and anesthetic. It is approximately 100 times more potent than morphine and 50 times more potent than heroin as an analgesic. Common street names include: Apache, China Girl, China Town, Dance Fever, Friend, Goodfellas, Great Bear, He-Man, Jackpot, King Ivory, Murder 8, and Tango & Cash. Fentanyl was first developed in 1959 and introduced in the 1960s as an intravenous anesthetic. Licit fentanyl pharmaceutical products are diverted via theft, fraudulent prescriptions, and illicit distribution by patients, physicians, and pharmacists. From 2005 through 2007, both fatal overdoses associated with abuse of clandestinely produced fentanyl and law enforcement encounters increased markedly. According to the Centers for Disease Control and Prevention, there were 1,013 fatal overdoses recorded from April 2005 to March 2007. More recently, there has been a re-emergence of trafficking, distribution, and abuse of illicitly produced fentanyl with an associated dramatic increase in overdose fatalities. Fentanyl pharmaceutical products are currently available in the following dosage forms: oral transmucosal lozenges commonly referred to as fentanyl "lollipops" (Actiq), effervescent buccal tablets (Fentora), sublingual tablets (Abstral), sublingual sprays (Subsys), nasal sprays (Lazanda), transdermal patches (Duragesic), and injectable formulations. Clandestinely produced fentanyl is encountered either as a powder or in counterfeit tablets and is sold alone or in combination with other drugs such as heroin or cocaine. Fentanyl can be injected, snorted/sniffed, smoked, taken orally by pill or tablet, and spiked onto blotter paper. Patches have also been frozen, cut into pieces, and placed under the tongue or in the cheek cavity. Illicitly produced fentanyl is sold alone or in combination with heroin and other substances and has been identified in counterfeit pills, mimicking pharmaceutical drugs such as oxycodone. According to the National Forensic Laboratory Information System, reports on fentanyl (both pharmaceutical and clandestinely produced) increased from nearly 5,400 in 2014 to over 14,600 in 2015, as reported by federal, state, and local forensic laboratories in the United States. Overdose may result in stupor, changes in pupillary size, cold and clammy skin, cyanosis, coma, and respiratory failure leading to death. Drugs that cause similar effects include other opioids such as morphine, hydrocodone, oxycodone, hydromorphone, methadone, and heroin. Heroin is processed from morphine, a naturally occurring substance extracted from the seed pod of certain varieties of poppy plants grown in: · Mexico, South America, Southwest Asia (Afghanistan and Pakistan), and Southeast Asia (Thailand, Laos, and Myanmar (Burma)) Heroin What is its effect on the body? As higher doses of the drug are used over time, physical dependence and addiction to the drug develop. Effects of heroin use include: · Drowsiness, respiratory depression, constricted pupils, nausea, a warm flushing of the skin, dry mouth, and heavy extremities Heroin comes in several forms, primarily white powder from Mexico and South America; and "black tar" and brown powder from Mexico. Common street names for heroin include: · Big H, Black Tar, Chiva, Hell Dust, Horse, Negra, Smack, and Thunder What does it look like? Heroin is typically sold as a white or brownish powder, or as the black sticky substance known on the streets as "black tar heroin. Because heroin users do not know the actual strength of the drug or its true contents, they are at a high risk of overdose or death. The effects of a heroin overdose are: · Slow and shallow breathing, blue lips and fingernails, clammy skin, convulsions, coma, and possible death How is it abused? Other opioids such as OxyContin, Vicodin, codeine, morphine, methadone, and fentanyl can cause similar effects as heroin. Because it enters the brain so rapidly, heroin is particularly addictive, both psychologically and physically. Heroin users report feeling a surge of euphoria or "rush," followed by a twilight state of sleep and wakefulness. Heroin is a Schedule I substance under the Controlled Substances Act meaning that it has a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision. Hydromorphone belongs to a class of drugs called "opioids," which includes morphine.
The aim of the second visit is to complete the debridement and remove the tissue remnants (Hasselgren, Olsson, and Cvek 1988). At the next appointment, if the barrier is incomplete and the patient feels the touch of a file, the apexification procedure is repeated until a complete barrier is formed. When an apical barrier is formed, a root canal filling is performed using either lateral condensation with Gutta Percha point or using the warm Gutta Percha technique (Rafter 2005). Apexification includes a coronal access that should be wide enough to include the pulp horns to prevent future contamination and discoloration. The length of the root canal in immature teeth can be determined radiographically and by using the paper point method. The debridement of the root canal should be done with minimal instrumentation to prevent damage to the thin dentin walls. Irrigation with disinfecting solutions should be done carefully, avoiding pushing the solutions beyond the apex. Twelve months post-op radiograph caretakers and the patient should bear in mind that this tooth may be lost in the future. CommonComplicationsandAlternative TreatmentPlans Common Complications · After apexification, the crown-root ratio is not favorable because the root is shorter than in a mature tooth; therefore, the prognosis of the tooth may be hampered. It was assumed that the size of the blunderbuss apex before treatment influenced the type and time of closure (Yates 1988). The frequency of fractures among immature teeth ranged from 77% in teeth with the least developed roots to 28% in teeth with the most developed roots. The prognosis may be further compromised by the placement of a temporary coronal seal (Tronstad et al. A histological and quantitative histomorphometric study of apexification of nonvital permanent incisors of vervet monkeys after repeated root filling with a calcium hydroxide paste. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta percha. Effects of calcium hydroxide and sodium hypochlorite on the dissolution of necrotic porcine muscle tissue. Soft tissue dissolution capacity of currently used and potential endodontic irrigants. Influence of coronal restorations on the periapical health of endodontically treated teeth. DentalHistory · Has a dental home · Eats a regular balanced diet · Fair oral hygiene habits, brushes his teeth twice a day unsupervised · Uses a fluoride-containing toothpaste · Lives in an optimally fluoridated area · Dental trauma at age 7 · Cooperative G. Intra-oralExam Soft Tissues · No significant findings Hard Tissues · No significant findings Occlusal Evaluation of Mixed Dentition · Class I permanent molars and primary canines, anterior crowding, overjet: 5 mm, overbite: 50% Dental Exam · Minimal plaque · Caries free · First permanent molars with amalgam restorations Figure 3. Obturation of the root canal can be done with a vertical condensation of warm Gutta Percha in the remainder of the canal. Periapical radiograph of the maxillary right permanent central incisor (arrow at radiolucent area) I. DiagnosticTools · Periapical radiograph of the maxillary right permanent central incisor (Figure 3. DifferentialDiagnosis · Remnants of the dental sac · Periapical true cyst · Non-odontogenic lesion K. ClinicalandRadiographicFollow-up · the tooth is asymptomatic and functional 12 months post-operatively (Figure 3. The size of the periapical radiolucency diminished; full healing is expected Figure 3. The tooth can be restored with minimal delay, preventing the risk of root fracture and re-infection. Radiograph showing obturation of the root canal 128 ClinicalCasesinPediatricDentistry N. PrognosisandDiscussion · Due to their thin dentinal walls, these teeth are prone to fracture. Therefore, a mouth guard is suggested to decrease the risk of injury in risky situations (sports, biking, etc. The post only retains the core and crown, but does not strengthen the tooth itself (Davy, Dilley, and Krejci 1981). Immature root filled teeth are often compromised by inappropriate post space preparation, coronal leakage, and secondary caries around prefabricated posts, or too large custom posts. It may be advantageous to use a light transmitting post and composite resin to internally strengthen the tooth (Sapir et al.
