The roles of acid-sensing ion channel 1a and ovarian cancer G protein-coupled receptor 1 on passive Mg2+ transport across intestinal epithelium-like Caco-2 monolayers

Intestinal passive Mg²⁺ absorption, which is vital for normal Mg²⁺ homeostasis, has been shown to be regulated by luminal proton. We aimed to study the regulatory role of intestinal acid sensors in paracellular passive Mg²⁺ transport. Omeprazole enhanced the expressions of acid-sensing ion channel 1a (ASIC1a), ovarian cancer G protein-coupled receptor 1 (OGR1), and transient receptor potential vanilloid 4 in Caco-2 cells. It also inhibited passive Mg²⁺ transport across Caco-2 monolayers. The expression and activation of OGR1 resulted in the stimulation of passive Mg²⁺ transport via phospholipase C- and protein kinase C-dependent pathways. ASIC1a activation, on the other hand, enhanced apical HCO₃ ^? secretion that led, at least in part, by a Ca²⁺-dependent pathway to an inhibition of paracellular Mg²⁺ absorption. Our results provided supporting evidence for the roles of OGR1 and ASIC1a in the regulation of intestinal passive Mg²⁺ absorption.     

Diving emergencies

Self-Contained Underwater Breathing Apparatus (SCUBA) diving popularity is increasing tremendously, reaching a total of 9 million people in the US during 2001, and 50,000 in the UK in 1985. Over the past 10 years, new advances, equipment improvements, and improved diver education have made SCUBA diving safer and more enjoyable. Most diving injuries are related to the behaviour of the gases and pressure changes during descent and ascent. The four main pathologies in diving medicine include: barotrauma (sinus, otic, and pulmonary); decompression illness (DCI); pulmonary edema and pharmacological; and toxic effects of increased partial pressures of gases. The clinical manifestations of a diving injury may be seen during a dive or up to 24 h after it. Physicians living far away from diving places are not excluded from the possibility of encountering diver-injured patients and therefore need to be aware of these injuries. This article reviews some of the principles of diving and pathophysiology of diving injuries as well as the acute treatment, and further management of these patients.     

Critical illness at mass gatherings is uncommon

Gatherings of large numbers of people at concerts, sporting events, and other occasions lead to an assembled population with a potential for a wide variety of illnesses and injuries. The collection of large numbers of people in a single location has led some authors to recommend the placement of resuscitation equipment or other medical services in close proximity to these activities. These recommendations not withstanding, data on the frequency of critical illness at mass gatherings (a group exceeding 1000 persons) are difficult to ascertain. Therefore, it was the purpose of this study to describe the incidence of critical illnesses among assembled populations at mass gatherings. An observational prospective study was conducted involving patient encounters at a large, multipurpose, indoor mass-gathering complex in Houston, Texas occurring between Septemver 1, 1996 and June 30, 1997. Demographic, treatment, disposition and diagnostic data were analyzed in a computerized database. Of the 3.3 million attendants to the 253 events analyzed during the 10-month study period, there were 2762 (0.08%) patient encounters. Fifty-two percent were women. Mean age was 32 ± 15.6 years. Of these patients, 51.1% were patrons and the remaining patients were employees or contractors of the facility. A wide variety of illness was seen with trauma (39.5%), headache (31%), and other medical complaints (29.5%) being most frequent. Disposition of the patients included 95.3% being discharged to go back to the event and 2.2% being counseled to seek other medical attention. One hundred twenty-nine patients (4.7%) were referred to the Emergency Department (ED); of these, 70 were transferred for abrasions, lacerations, or skeletal injuries and 13 for chest pain. Of those referred to the ED, 50 (38.7%) patients were transported by ambulance and only 17.4% were admitted to telemetry, with none admitted to an ICU. It is concluded that critical illness at mass gatherings is infrequent, as seen in this study, with very few being admitted to telemetry and none to an ICU. Careful consideration of cost-benefit should occur when determining allocation of resources for these activities.     

Deregulation of intestinal anti-microbial defense by the dietary additive,maltodextrin

Inflammatory bowel disease (IBD) is a complex, multi-factorial disease thought to arise from an inappropriate immune response to commensal bacteria in a genetically susceptible person that results in chronic, cyclical, intestinal inflammation. Dietary and environmental factors are implicated in the initiation and perpetuation of IBD; however, a singular causative agent has not been identified. As of now, the role of environmental priming or triggers in IBD onset and pathogenesis are not well understood, but these factors appear to synergize with other disease susceptibility factors. In previous work, we determined that the polysaccharide dietary additive, maltodextrin (MDX), impairs cellular anti-bacterial responses and suppresses intestinal anti-microbial defense mechanisms. In this addendum, we review potential mechanisms for dietary deregulation of intestinal homeostasis, postulate how dietary and genetic risk factors may combine to result in disease pathogenesis, and discuss these ideas in the context of recent findings related to dietary interventions for IBD.     

Novel and de-novo truncating PAX6 mutations and ocular phenotypes in Thai aniridia patients

PURPOSE: To describe the ophthalmic findings and mutation analyses of the PAX6 gene in Thai aniridia patients. METHODS: Ten patients from six unrelated families underwent a comprehensive ophthalmic examination. Mutations in the PAX6 gene were screened by single-strand conformational polymorphism (SSCP) and direct DNA sequencing of the SSCP variants. RESULTS: Seven patients developed cataracts and six developed glaucoma. Mutation analysis demonstrated four different truncating mutations, two of which were de novo. These included one novel insertion/deletion mutation (c.474del12insGA in exon 5) and three nonsense mutations. R203X and R240X are common recurrent mutations, while Q277X in exon 10 is novel. All mutations resulted in loss of function of the PAX6 protein. CONCLUSION: Our data confirm inter- and intrafamilial variable phenotypic manifestations of which the underlying mechanisms may be haploinsufficiency or dominant-negative mutation.