5-HT-receptor-induced changes of the intracellular cAMP level monitored by a hyperpolarization-activated cation channel

The HvCNG channel from the moth Heliothis virescens is highly sensitive to cAMP concentrations ranging between 0.1 microM and 5 microM. This HvCNG channel was over-expressed in Spodoptera frugiperda (Sf.9) cells to measure endogenous cAMP levels. Hyperpolarization-activated inward currents were measured in the whole-cell patch-clamp configuration with pipettes filled with different cAMP concentrations to calibrate the system. Varying the cAMP concentration between 0 microM and 100 microM in the pipette, the half-maximal activation voltage ( V1/2) was shifted by +28.5+/-1.7 mV. The activation time constant (tau(a)) was used as a parameter for cAMP quantification because it was independent of the expression level of HvCNG channels. tau(a) changed from 1106+/-60 ms at 0 microM cAMP to 265+/-7 ms at a saturating concentration of 1 mM cAMP. A dose-response relationship yielded values of 0.6 microM for the half-maximal cAMP concentration and 1.5 for the Hill coefficient. Activation of endogenous adenylyl cyclases by 50 microM forskolin induced an elevation of the cAMP level by about 1.6+/-0.2 microM. Co-expressions of HvCNG channels in combination with the mouse 5-HT4a- or 5-HT1A- receptors and the corresponding Gs- or Gi-proteins were successful and allowed us to also verify receptor-induced changes of the cAMP level. Stimulation of m5-HT4a-receptors by 0.1 microM 5-HT induced an increase of cAMP of about 4.6+/-1.5 microM, whereas cAMP levels decreased from a control value of 1+/-0.2 microM to 0.41+/-0.1 microM after stimulation of the m5-HT1A-receptors.     

Three-Dimensional Soft Tissue Prediction Using Finite Elements

BACKGROUND AND AIM: The goal of this study was to analyze the validity and prediction accuracy of a newly-developed procedure for three-dimensional soft tissue prediction based on Finite Element Method, and to compare the results with prediction produced using an existing two-dimensional prediction program (Dentofacial Planner Plus). PATIENTS AND METHODS: In twelve patients who underwent combined surgical-orthodontic treatment, profile prediction was generated using both procedures preoperatively and then compared at predefined measurement points with the patient's actual postoperative soft tissue status. RESULTS: The deviations observed depended on the facial region, whereby the prediction errors for both procedures were much greater in the lower facial third than in the midfacial third. Calculating in all the measurement points, the mean horizontal prediction error was 0.32 mm for the Finite Element Method and 0.75 mm for the Dentofacial Planner Plus. Overall, we were able to demonstrate the new procedure's superior validity and quality of visualization. In addition to profile prediction, the procedure allows a differentiated three-dimensional assessment of esthetically important regions such as the cheeks, nasolabial folds and the nasal wings. Additional X-radiation is not necessary in this risk-free and stress-free procedure. CONCLUSION: Three-dimensional soft tissue prediction employing finite element modeling is a useful aid for implementing esthetically-optimized treatment planning.     

Incretin mimetics as a novel therapeutic option for hepatic steatosis.

BACKGROUND: Fat accumulation in the liver or non-alcoholic fatty liver disease (NAFLD) is regarded as a key pathogenic factor and component of the metabolic syndrome. It was reported that administration of the incretin mimetic exenatide reversed hepatic steatosis in an obese mouse model. We had the opportunity to study the effect of additional exenatide administration on liver fat content in a patient with type 2 diabetes. CASE REPORT: A 59-year-old male with poorly controlled type 2 diabetes was treated with exenatide in addition to metformin monotherapy. Following 44 weeks of exenatide therapy, mean the liver fat measured by liver spectroscopy declined from 15.8% to 4.3%. This dramatic decrease in liver fat was accompanied by significant beneficial changes in several cardiovascular disease risk factors and improvement of all liver enzymes, in particular alanine aminotransferase, the most important marker of liver steatosis. CONCLUSION: This case report suggests that the incretin mimetic exenatide decreases hepatic fat accumulation and may play a role in the future treatment of NAFLD, and the associated insulin resistance and cardiovascular risk factors in an ever-growing high-risk population.     

Comparison of three different purification methods for the routine preparation of [11C] Metomidate.

PET with (R)-[O-methyl-11C] metomidate ([11C] MTO) is an attractive method for the characterisation of adrenal masses discriminating lesions of adrenal cortical origin from noncortical lesions. [11C] MTO was prepared by the reaction of [11C] methyliodide with the corresponding free acid. Three purification methods have been compared. The method of choice uses preparative HPLC with a ready-to-use weak acidic solvent.     

Lack of interaction between diazepam and nimodipine during chronic oral administration to healthy elderly subjects.

1. Nimodipine (30 mg three times daily) and diazepam (10 mg once daily), were given orally to 24 elderly healthy subjects in a randomized, non-blinded, threefold-crossover study. Each of the three treatment periods lasted 5 days separated by 2 week washout phases. 2. Plasma concentrations of nimodipine and diazepam were not affected by the combined treatment. 3. No clinically relevant changes in haemodynamics, ECG recordings, clinical chemistry or haematology were observed after all of the three treatments. The overall frequency of side effects was lowest during monotherapy with nimodipine and highest during diazepam monotherapy. 4. In the test of subjective rating of tiredness (VAS) and the Pauli calculation test, diazepam, alone and with nimodipine co-medication, produced an increase in tiredness and a clear reduction in performance and endurance. After nimodipine monotherapy an improvement was observed only in the Pauli test. Using the critical flicker fusion frequency test (CFF) significant decrements in performance were found after diazepam monotherapy only. 5. In summary, there was no evidence that either nimodipine or diazepam affected the pharmacokinetics, safety and tolerance of each other. However, the CNS-effects of diazepam were compensated partially by nimodipine.     

Gram-negative bacterial pneumonia with secondary aspergillosis in an AIDS patient

Summary A 40-year-old, HIV-infected female patient received antibiotic treatment for a urinary tract infection. After the initial success of therapy and a symptom-free period, she developed pneumonia with septic shock and adult respiratory distress syndrome (ARDS). In spite of intensive care and respirator therapy with positive end-expiratory pressure (PEEP), she died of infectious toxic shock. Autopsy findings showed relapsing, gramnegative, bacterial pneumonia (morphologically compatible with Klebsiella pneumonia) and secondary, invasive aspergillosis. The pathogenesis and epidemiology of these unusual complications of AIDS are discussed.Abbreviations AIDS acquired immunodeficiency syndrome - ARDS adult respiratory distress syndrome - CDC Centers for Disease Control - HIV human immunodeficiency virus - PEEP positive end-expiratory pressure     

Nocturnal hypoglycaemia in Type 1 diabetic patients,assessed with continuous glucose monitoring: frequency,duration and associations

Aims We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple‐injection therapy (MIT) using a continuous subcutaneous glucose sensor. Methods A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA_1c 7.8 ± 0.9%) and 33 patients on MIT (HbA_1c 8.7 ± 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA_1c, diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated. Results Nocturnal hypoglycaemia ≤ 3.9 mmol/l occurred in 33.3% of both the CSII‐ (8/24) and MIT‐treated patients (11/33). Mean (± sd ; median, interquartile range) duration of hypoglycaemia ≤ 3.9 mmol/l was 78 (± 76; 57, 23–120) min per night for the CSII‐ and 98 (± 80; 81, 32–158) min per night for the MIT‐treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia. Conclusions Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.     

Sustained good glycaemic control in NIDDM patients by implementation of structured care in general practice: 2-year follow-up study

Summary In primary care it is difficult to treat the growing number of non-insulin-dependent diabetic (NIDDM) patients according to (inter)national guidelines. A prospective, controlled cohort study was designed to assess the intermediate term (2 years) effect of structured NIDDM care in general practice with and without ’diabetes service' support on glycaemic control, cardiovascular risk factors, general well-being and treatment satisfaction. The ’diabetes service', supervised by a diabetologist, included a patient registration system, consultation facilities of a dietitian and diabetes nurse educator, and protocolized blood glucose lowering therapy advice which included home blood glucose monitoring and insulin therapy. In the study group (SG; 22 general practices), 350 known NIDDM patients over 40 years of age (206 women; mean age 65.3 ± SD 11.9; diabetes duration 5.9 ± 5.4 years) were followed for 2 years. The control group (CG; 6 general practices) consisted of 68 patients (28 women; age 64.6 ± 10.3; diabetes duration 6.3 ± 6.4 years). Mean HbA_{1 c} (reference 4.3–6.1 %) fell from 7.4 to 7.0 % in SG and rose from 7.4 to 7.6 % in CG during follow-up (p = 0.004). The percentage of patients with poor control (HbA_{1 c} > 8.5 %) shifted from 21.4 to 11.7 % in SG, but from 23.5 to 27.9 % in CG (p = 0.008). Good control (HbA_{1 c} < 7.0 %) was achieved in 54.3 % (SG; at entry 43.4 %) and 44.1 % (CG; at entry 54.4 %) (p = 0.013). Insulin therapy was started in 29.7 % (SG) and 8.8 % (CG) of the patients (p = 0.000) with low risk of severe hypoglycaemia (0.019/patient year). Mean levels of total and HDL-cholesterol (SG), triglycerides (SG) and diastolic blood pressure (SG + CG) and the percentage of smokers (SG) declined significantly, but the prevalence of these risk factors remained high. General well-being (SG) did not change during intensified therapy. Treatment satisfaction (SG) tended to improve. Implementation of structured care, including education and therapeutic advice, results in sustained good glycaemic control in the majority of NIDDM patients in primary care, with low risk of hypoglycaemia. Lowering cardiovascular risk requires more than reporting results and referral to guidelines. [Diabetologia (1997) 40: 1334–1340] Received: 5 February 1997 and in revised form: 22 May 1997     

Extraction of an artery in rectal biopsy]

A biopsy of a rectal carcinoma has led to the extraction of a 2.5 cm arterial specimen, followed by an arterial bleeding. The cause of this exceptional complication was the presence of atypical vessels reaching the rectal lumen due to tumor ulceration.