Inhibition of inflammatory pain by CRF at peripheral, spinal and supraspinal sites: involvement of areas coexpressing CRF receptors and opioid peptides.

There is conflicting evidence on the antinociceptive effects of corticotropin-releasing factor (CRF) along the neuraxis of pain transmission and the responsible anatomical sites of CRF's action at the level of the brain, spinal cord and periphery. In an animal model of tonic pain, that is, Freunds complete adjuvant (FCA) hindpaw inflammation, we systematically investigated CRF's ability to modulate inflammatory pain at those three levels of pain transmission by algesiometry following the intracerebroventricular, intrathecal, and intraplantar application of low, systemically inactive doses of CRF. At each level, CRF elicits potent antinociceptive effects, which are dose dependent and antagonized by local, but not systemic CRF receptor antagonist alpha-helical CRF indicating CRF receptor specificity. Consistently, we have identified by immunohistochemistry multiple brain areas, inhibitory interneurons within the dorsal horn of the spinal cord as well as immune cells within subcutaneous tissue--but not peripheral sensory neurons--that coexpress both CRF receptors and opioid peptides. In line with these anatomical findings, local administration of CRF together with the opioid receptor antagonist naloxone dose-dependently reversed CRF's antinociceptive effects at each of these three levels of pain transmission. Therefore, local application of low, systemically inactive doses of CRF at the level of the brain, spinal cord and periphery inhibits tonic inflammatory pain most likely through an activation of CRF receptors on cells that coexpress opioid peptides which results in opioid-mediated pain inhibition. Future studies have to delineate whether endogenous CRF at these three levels contributes to the body's response to cope with the stressful stimulus pain in an opioid-mediated manner.     

Very Early Onset of Wernicke's Encephalopathy after Gastric Bypass

Postoperative complications resulting from bariatric surgery can lead to severe vitamin-deficiency states, such as Wernicke's encephalopathy (WE). We present a 29-year-old woman with BMI 41.7 with no history of alcoholism who developed acute WE after a gastric bypass for morbid obesity. After persistent vomiting for 2 weeks postoperatively, symptoms began with headache, vertigo, diplopia, nystagmus, tingling and weakness in both upper and lower extremities, urinary incontinence, and memory loss to recent events. All investigations, including upper GI endoscopy, Gastrografin meal and even MRI, were normal. A dramatic improvement occurred in 24 hrs after starting 100 mg thiamine infusion daily. We recommend that patients undergoing bariatric surgery should be started on thiamine supplementation once oral intake begins, because this case showed that postoperative acute WE can develop before 6 weeks, unlike other reports.     

Perceived sources of stress within a dental educational environment

The aim of this study was to identify the perceived sources of stress among dental students, dental hygiene students, and dental technology students enrolled at Jordan University of Science and Technology (JUST). The modified dental environment stress questionnaire was administered to 183 students. The perceived stressors varied between major and year. Dental students gave high scores for examinations, reduced holidays, inadequate time for relaxation, fear of failure, completing clinical requirements, and differences in opinion between staff. Dental hygiene students gave the highest scores for uncertainty about the field of study as future career, examinations, inadequate clinical training and supervision, inadequate relaxation, and discrimination between students. Dental technology students also gave high scores for uncertainty about future career, examinations, approachability of the staff, inadequate relaxation, and completing requirements. Females are more stressed than males with regard to personal factors. Dental technology and/or dental hygiene students have significantly higher scores than dental students in 12 items. Students who reported their first choice of study was not their current field of study showed more stress concerning their future careers. The high scores reported for some stressors among students emphasize the need to address student's concerns.     

Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis

Integrin alpha(V)beta(3) is a heterodimeric plasma membrane protein whose several extracellular matrix protein ligands contain an RGD recognition sequence. This study identifies integrin alpha(V)beta(3) as a cell surface receptor for thyroid hormone [L-T(4) (T(4))] and as the initiation site for T(4)-induced activation of intracellular signaling cascades. Integrin alpha(V)beta(3) dissociably binds radiolabeled T(4) with high affinity, and this binding is displaced by tetraiodothyroacetic acid, alpha(V)beta(3) antibodies, and an integrin RGD recognition site peptide. CV-1 cells lack nuclear thyroid hormone receptor, but express plasma membrane alpha(V)beta(3); treatment of these cells with physiological concentrations of T(4) activates the MAPK pathway, an effect inhibited by tetraiodothyroacetic acid, RGD peptide, and alpha(V)beta(3) antibodies. Inhibitors of T(4) binding to the integrin also block the MAPK-mediated proangiogenic action of T(4). T(4)-induced phosphorylation of MAPK is inhibited by small interfering RNA knockdown of alpha(V) and beta(3). These findings suggest that T(4) binds to alpha(V)beta(3) near the RGD recognition site and show that hormone-binding to alpha(V)beta(3) has physiological consequences.     

Rhinocerebral mucormycosis: pathways of spread

Rhinocerebral mucormycosis is an invasive, opportunistic fungal infection usually seen in immunocompromised patients, and particularly in the setting of diabetes or immune deficiency. It is assumed that the port of entry is colonization of the nasal mucosa, allowing the fungus to spread via the paranasal sinuses into the orbit. Involvement of the brain and cavernous sinus occurs by way of the orbital apex; therefore, spheno-ethmoidectomy with or without maxillectomy seems to be the definitive method to eradicate this infection. We conducted a prospective study of ten patients with rhinocerebral mucormycosis from February 2000 to April 2004. Rhinocerebral mucormycosis was clinically diagnosed in 11 patients, 10 of whom were included in our study upon histopathological confirmation. Diabetes was the most common underlying disorder seen in nine out of ten patients. In this study, the patients were assessed for predisposing factors, presenting signs and symptoms, sites of extension, the number and sites of surgical debridement, as well as the outcome. Ocular, sinonasal and facial soft tissue involvement was common. Involvement of the pterygopalatine fossa at the time of debridement was evident in all patients. No invasion through the lamina papiracea or the walls of the maxillary sinus was identified. At the time of this communication, six out of ten patients were alive. For the four who died, the causes were hypokalemia, cardiac arrythmia and refractory pneumonia. Pterygopalatine fossa is considered to be the main reservoir for rhinocerebral mucormycosis, and extension into the orbit and facial soft tissues usually follows this route. After proliferation in the nasal cavity, the mucor reaches the pterygo-palatine fossa, inferior orbital fissure and finally the retroglobal space of the orbit, resulting in ocular signs. The facial soft tissues, palate and infratemporal fossa can be infected through connecting pathways from the pterygo-palatine fossa; therefore, debridement of the pterygopalatine fossa seems to be the definitive method of managing this infection.     

Child mental health problems in the Gaza Strip

This study describes the mental health characteristics of 150 children of 6-13 years of age, who had been referred to different types of services in the Gaza Strip: a community mental health center, five primary health centers and a pediatric hospital. There was a high rate of somatising disorders among children referred to the mental health center (42%). Parent-reported rates of significant mental health problems were high for all groups, i.e., 70% in the mental health center group, 30% in the pediatric group, and 18% among children referred to primary health centers.     

Effect of dimethyl sulfoxide on gentamicin-induced nephrotoxicity in rats

Nephrotoxicity of gentamicin (GM) has been suggested to be mediated by the generation of reduced oxygen metabolites. The present study investigated the possible protective role of the free radical scavenger dimethyl sulfoxide (DMSO) on some indices of GM nephrotoxicity in rats. The antibiotic was injected intramuscularly (i.m.) at a dose of 100 mg/kg for six consecutive days, either with or without treatment with DMSO (12.5%, 25% or 50% in saline) at an intraperitoneal (i.p.) dose of 2 ml/kg 4 days before GM, and concomitantly with GM treatment thereafter. DMSO (25% in saline) was also given as above to rats treated with GM at i.m. doses of 25, 50 or 100 mg/kg for six consecutive days. GM caused dose-dependent significant increases in the concentrations of urea and creatinine in plasma, and in thiobarbituric acid reactive substances (TBARS) level in the kidney cortex and also caused significant decreases in the concentrations of reduced glutathione (GSH) and superoxide dismutase (SOD) activity. In GM-treated rats, DMSO dose-dependently lowered the elevated plasma urea and creatinine concentrations, and the rise in cortical TBARS. It also restored the levels of GSH and SOD activity to near normal. DMSO (25%) was effective in completely preventing the development of signs of nephrotoxicity of G (50 mg/kg). Treatment of the rats with DMSO alone, at any of the above doses, did not alter significantly any of the renal or hepatic function tests studied, and did not appear to adversely affect the kidney or liver histology. However, the efficacy and safety of DMSO require further studies. It is suggested that DMSO has potential protective effect against GM nephrotoxicity in rats.