Rescue of defective G protein–coupled receptor function in vivo by intermolecular cooperation

G protein–coupled receptors (GPCRs) are ubiquitous mediators of signaling of hormones, neurotransmitters, and sensing. The old dogma is that a one ligand/one receptor complex constitutes the functional unit of GPCR signaling. However, there is mounting evidence that some GPCRs form dimers or oligomers during their biosynthesis, activation, inactivation, and/or internalization. This evidence has been obtained exclusively from cell culture experiments, and proof for the physiological significance of GPCR di/oligomerization in vivo is still missing. Using the mouse luteinizing hormone receptor (LHR) as a model GPCR, we demonstrate that transgenic mice coexpressing binding-deficient and signaling-deficient forms of LHR can reestablish normal LH actions through intermolecular functional complementation of the mutant receptors in the absence of functional wild-type receptors. These results provide compelling in vivo evidence for the physiological relevance of intermolecular cooperation in GPCR signaling.     

Oncocytic Cell Tumors of the Thyroid: Factors Predicting Malignancy and Influencing Prognosis, Treatment Decisions, and Outcomes

Background  

The distinction between malignant and benign thyroid oncocytic cell tumors (OCTs) before and during surgery still represents a diagnostic challenge. We focused on the search for specific factors that predict malignancy and influence the prognosis of OCTs, and for their most appropriate management.     

Oral distribution of Candida species and presence of oral lesions in Brazilian leprosy patients under multidrug therapy

Objective:  The aim of this study was to evaluate the prevalence of Candida spp. and presence of oral lesions in Brazilian leprosy patients under multidrug therapy (MDT).
Methods:  Thirty-eight individuals (18 males and 20 females, median age 53 years) clinically and microbiologically diagnosed as leprosy (lepromatous variant), and under MDT for at least 45 days were studied. The control group constituted by 38 healthy individuals (median age 53.5), matched to the test group in relation to age, gender and oral conditions. Oral rinses were collected and the Candida identification was performed by phenotypic tests. The existence of Candida dubliniensis among the isolates was analyzed using a validated multiplex PCR assay. Twenty-nine leprosy patients were examined intra-orally for the presence of lesions. Data were analyzed by z- and Mann–Whitney tests (α = 5%).
Results:  Yeast carriage rate between leprosy patients (65.8%) and controls (47.4%) was similar ( P  = 0.099), and no significant difference between yeast counts was observed ( P  = 0.1004). Candida albicans was the most frequently isolated species in both groups. In the leprosy group, Candida tropicalis and Candida parapsilosis were also identified. In the control group, we additionally identified Candida tropicalis , Candida glabrata and Candida kefyr. Candida dubliniensis was not detected. No leprosy-related oral lesion was registered.
Conclusion:  Within the limits of the study, we concluded that Brazilian leprosy patients under MDT showed similar levels of carriage and Candida species distribution in relation to the controls.     

New and Low-Cost Auto-Algometry for Screening Hypertension-Associated Hypoalgesia

Objective:   The aim of the present work was to measure the pain threshold in hypertensive patients with a new auto-algometry method.
Design and Setting:   Auto-algometry consists of asking the subjects to push their fingers against a fixed round-tip needle until they feel a pain sensation. An electronic force transducer permits the measurement of the force applied by the subjects and storage of the data on a personal computer. Eight tests are performed twice on each subject on the tip and back of four fingers. For each test, the maximal applied force (grams) is defined as pain threshold. The overall discomfort during the entire procedure is reported by the subjects on a 0 (no discomfort) to 10 (intolerable pain) scale.
Patients and Interventions:   A group of hypertensive patients ( n  = 22) and a group of normotensive subjects ( n  = 22) underwent the auto-algometry examination.
Results:   The pain threshold was higher in hypertensive patients compared with normotensive subjects. All discomfort scores referred by the subjects fell within the 4–6 range.
Conclusion:   The data obtained from this study indicate that the auto-algometer as described here can detect hypoalgesia associated with hypertension.