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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CB1 cannabinoid receptor is a G-protein coupled receptor that has important physiological roles in synaptic plasticity, analgesia, appetite, and neuroprotection. We report the discovery of two structurally related CB1 cannabinoid receptor interacting proteins (CRIP1a and CRIP1b) that bind to the distal C-terminal tail of CB1. CRIP1a and CRIP1b are generated by alternative splicing of a gene located on chromosome 2 in humans, and orthologs of CRIP1a occur throughout the vertebrates, whereas CRIP1b seems to be unique to primates. CRIP1a coimmunoprecipitates with CB1 receptors derived from rat brain homogenates, indicating that CRIP1a and CB1 interact in vivo. Furthermore, in superior cervical ganglion neurons coinjected with CB1 and CRIP1a or CRIP1b cDNA, CRIP1a, but not CRIP1b, suppresses CB1-mediated tonic inhibition of voltage-gated Ca2+ channels. Discovery of CRIP1a provides the basis for a new avenue of research on mechanisms of CB1 regulation in the nervous system and may lead to development of novel drugs to treat disorders where modulation of CB1 activity has therapeutic potential (e.g., chronic pain, obesity, and epilepsy).
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PMID:CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a. 1789 7

For thousands of years mu opioid agonists such as morphine have been utilized for their analgesic properties. Today, morphine and related compounds are still used as a first line therapy in the treatment of moderate to severe pain. However, despite the clear benefits of mu agonists in pain management, severe side effects such as dependence and respiratory depression are associated with use of these drugs. To date, there are only two approved mu opioid antagonists for use in the treatment of these adverse effects, that is, naloxone and naltrexone. However, many other clinical and therapeutic areas have been linked to mu opioid receptor antagonism. These include treatment of opioid induced pruritus of the skin, obesity, and Parkinson-induced tardive dyskinesia. Currently there are two compounds, N-methylnaltrexone and alvimopan, under FDA review as possible treatments for opioid induced bowel dysfunction and postoperative ileus. These compounds are of special interest as they are peripherally restricted. This attribute enables treatment of peripheral side effects induced by opioid agonists without reversal of the centrally mediated analgesia of the agonist. In this article we discuss the structural classes of mu opioid antagonists, their potential clinical applications, and review the relevant patents of the last ten years.
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PMID:Mu opioid receptor antagonists: recent developments. 1791 59

Gastrin and cholecystokinin (CCK) are two of the oldest hormones and within the past 15 years there has been an exponential increase in knowledge of their pharmacology, cell biology, receptors (CCK1R and CCK2R), and roles in physiology and pathological conditions. Despite these advances there is no approved disease indication for CCK receptor antagonists and only a minor use of agonists. In this review, the important factors determining this slow therapeutic development are reviewed. To assess this it is necessary to briefly review what is known about the roles of CCK receptors (CCK1R and CCK2R) in normal human physiology, their role in pathologic conditions, the selectivity of available potent CCKR agonists/antagonists as well as to review their use in human conditions to date and the results. Despite extensive studies in animals and in humans, recent studies suggest that monotherapy with CCK1R agonists will not be effective in obesity, nor CCK2R antagonists in panic disorders or CCK2R antagonists to inhibit growth of pancreatic cancer. Areas that require more study include the use of CCK2R agonists for imaging tumors and radiotherapy, CCK2R antagonists in hypergastrinemic states especially with long-term PPI use and for potentiation of analgesia as well as use of CCK1R antagonists for a number of gastrointestinal disorders [motility disorders (irritable bowel syndrome, dyspepsia, and constipation) and pancreatitis (acute and chronic)].
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PMID:Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have therapeutic potential. 1799 37

The potential advantages of regional anesthesia include minimal airway intervention, less cardiopulmonary depression, excellent postoperative analgesia, less postoperative nausea and vomiting, and shorter recovery room and hospital stays. These concerns are particularly important for the obese surgical patient. This review discusses the application of regional anesthetic techniques in obesity. Further clinical studies are needed to fill the knowledge gap about regional anesthesia and outcome in obese and morbidly obese patients.
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PMID:Regional anesthesia and obesity. 1807 86

Acquired adult flatfoot deformity is a commonly encountered entity in orthopaedic practice. It results mainly from posterior tibial tendon (PTT) dysfunction, is more common in women and frequently associated with obesity. The four severity stages are based on dysfunction of the PTT, on the reducibility of the deformity, and on the condition of the hindfoot joints. Conservative treatment is functionally efficient in the early stages and may also contribute to analgesia in advanced stages. The goal of surgery is to restore a functional mobility in the early stages and to achieve rigid stabilization of the hindfoot in the late stages. The treatment's choice and the control of the predisposing factors for acquired flatfoot depends upon a close collaboration between the family physician and the orthopaedic surgeon.
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PMID:[Acquired adult flatfoot deformity: a pragmatic approach]. 1827 65

The active component of the marijuana plant Cannabis sativa, Delta9-tetrahydrocannabinol (THC), produces numerous beneficial effects, including analgesia, appetite stimulation and nausea reduction, in addition to its psychotropic effects. THC mimics the action of endogenous fatty acid derivatives, referred to as endocannabinoids. The effects of THC and the endocannabinoids are mediated largely by metabotropic receptors that are distributed throughout the nervous and peripheral organ systems. There is great interest in endocannabinoids for their role in neuroplasticity as well as for therapeutic use in numerous conditions, including pain, stroke, cancer, obesity, osteoporosis, fertility, neurodegenerative diseases, multiple sclerosis, glaucoma and inflammatory diseases, among others. However, there has been relatively far less research on this topic in the eye and retina compared with the brain and other organ systems. The purpose of this review is to introduce the "cannabinergic" field to the retinal community. All of the fundamental works on cannabinoids have been performed in non-retinal preparations, necessitating extensive dependence on this literature for background. Happily, the retinal cannabinoid system has much in common with other regions of the central nervous system. For example, there is general agreement that cannabinoids suppress dopamine release and presynaptically reduce transmitter release from cones and bipolar cells. How these effects relate to light and dark adaptations, receptive field formation, temporal properties of ganglion cells or visual perception are unknown. The presence of multiple endocannabinoids, degradative enzymes with their bioactive metabolites, and receptors provides a broad spectrum of opportunities for basic research and to identify targets for therapeutic application to retinal diseases.
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PMID:Endocannabinoids in the retina: from marijuana to neuroprotection. 1872 16

Regional anesthesia has an expanding role in upper extremity surgery. Brachial plexus blocks offer several advantages including providing effective analgesia, reducing narcotic requirements, and facilitating ambulatory care surgery. Despite the popularity of nerve blocks, the surgeon must not forget the complications associated with regional anesthesia. This article describes a case of symptomatic phrenic nerve palsy after supraclavicular brachial plexus block in an obese man. A 46-year-old obese man underwent a left-sided supraclavicular block in preparation for decompression of Guyon's canal for ulnar mononeuropathy at the wrist. The patient experienced acute-onset dyspnea, chest discomfort, and anxiety, and physical examination demonstrated reduced breath sounds in the left hemithorax. Chest radiographs documented elevation of the left hemidiaphragm consistent with an iatrogenic phrenic nerve palsy. The patient was admitted for 23-hour observation and underwent an uncomplicated ulnar nerve decompression under Bier block anesthesia 1 week later. No long-term sequelae have been identified; however, there was a delay in surgical care, admission to the hospital, and transient pulmonary symptoms. We attribute this complication to significant abdominal obesity causing compromised pulmonary reserve and poor tolerance of transient hemidiaphragmatic paresis. In recent studies, waist circumference and abdominal height were inversely related to pulmonary function. We suspect that the incidence of symptomatic phrenic nerve palsy associated with brachial plexus blocks will increase as the prevalence of obesity increases in this country.
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PMID:Symptomatic phrenic nerve palsy after supraclavicular block in an obese man. 1947 48

The function of the endogenous analgesia system under natural circumstances has been little explored. Our recent work shows that animals are significantly less responsive to noxious stimulation during slow wave sleep, micturition, and while eating than during quiet wake. The analgesia associated with eating is dependent on activity in the medullary raphe magnus, the final common brain stem region in endogenous analgesia pathways. Eating analgesia does not depend on energy-depletion due to food deprivation. Further, analgesia accompanies chow-eating even though chow has no sucrose, demonstrating that sucrose is not a necessary component of analgesia-evoking ingestates. Since raphe magnus modulates processing of innocuous as well as nociceptive information, the sensory suppression accompanying eating is likely a more general depression of the response to external stimulation. Such a phenomenon would serve animals well under natural conditions where energy-dense food is scarce but has counterproductive effects, possibly contributing to obesity, in modern human society where energy-dense food is readily available.
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PMID:Food consumption inhibits pain-related behaviors. 1968 66

Epidural analgesia provides effective control of labor pain and allows emergency cesarean section to be performed without recourse to general anesthesia. This technique is subject to failure, however. We sought to determine the incidence of failure of extension of epidural analgesia for labor to epidural anesthesia for emergency cesarean section. We also analyzed possible risk factors for failure. A 2-month observational study was carried out in a tertiary-care university hospital in patients who had an epidural catheter inserted for labor analgesia and who later underwent emergency cesarean section. Epidural catheter failure was defined if additional analgesia was required during surgery or if general anesthesia was required. Data were gathered on possible risk factors, such as obesity, difficult epidural puncture, leakage of blood on insertion, history of cesarean delivery, need for rescue analgesia, and level of satisfaction with analgesia during dilation. In total, 134 emergency cesareans were performed in women carrying an epidural catheter. The catheter failed to administer the anesthetic in 18 patients (13.4%). General anesthesia was required in 9 cases (6.7%). Difficult insertion (more than 2 attempts) was associated with a higher failure rate (P=.064). The relative risk of epidural catheter failure was 2.86-fold higher when rescue analgesia was needed during delivery than in cases when no supplement was required (P=.021). Receiving adequate analgesia during labor seems to be a protective factor (80%) against anesthetic catheter failure during cesarean section (P=.01). We conclude that high demand for rescue analgesia and signs of inadequate analgesia during labor should warn of epidural catheter failure if extension to anesthesia becomes necessary for a cesarean delivery.
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PMID:[Failure of extension of epidural analgesia to anesthesia for emergency cesarean section]. 1985 87

As the epidemics of obesity and diabetes expand, there are more patients with these disorders requiring elective surgery. For surgery on the extremities, peripheral nerve blocks have become a highly favorable anesthetic option when compared with general anesthesia. Peripheral blocks reduce respiratory and cardiac stresses, while potentially mitigating untreated peripheral pain that can foster physiologic conditions that increase risks for general health complications. However, local anesthetics are generally accepted to be a rare but possible cause of nerve damage, and there are no evidence-based recommendations for dosing local anesthetic nerve blocks in patients with diabetes. This is important because anesthesiologists do not want to potentially accelerate peripheral nerve dysfunction in diabetic patients at risk. This translational vignette (i) examines laboratory models of diabetes, (ii) summarizes the pharmacology of perineural adjuvants (epinephrine, clonidine, buprenorphine, midazolam, tramadol, and dexamethasone), and (iii) identifies areas that warrant further research to determine viability of monotherapy or combination therapy for peripheral nerve analgesia in diabetic patients. Conceivably, future translational research regarding peripheral nerve blocks in diabetic patients may logically include study of nontoxic injectable analgesic adjuvants, in combination, to provide desired analgesia, while possibly avoiding peripheral nerve toxicity that diabetic animal models have exhibited when exposed to traditional local anesthetics.
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PMID:Future considerations for pharmacologic adjuvants in single-injection peripheral nerve blocks for patients with diabetes mellitus. 1992 Apr 20


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