cis- and trans-Resveratrol are glucuronidated in rat brain, olfactory mucosa and cultured astrocytes

BACKGROUND/AIMS: Glucuronidation of cis- and trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene), which is a naturally occurring phytoalexin known to exert a number of beneficial health effects, was investigated in rat brain, cultured astrocytes and olfactory mucosa. METHODS: The isomers were incubated with tissue homogenates, microsomes, or rat liver recombinant UDP-glucuronosyltransferases in the presence of UDP-glucuronic acid. The glucuronides were separated by HPLC and quantitated. Astrocytes were exposed to lipopolysaccharide to promote inflammatory conditions. RESULTS: All tissues were able to form resveratrol glucuronides although at a lower extent, when compared to the liver. The reaction was stereo- and regioselective. In brain tissue, trans-resveratrol 3-O-glucuronide was mainly formed, whereas the cis-isomer was glucuronidated at a lower rate on that position. No 4'-O-glucuronide was detected in brain. In olfactory mucosa homogenates, the cis 3-O-glucuronide was mainly formed, whereas the trans-isomer was glucuronidated only on the 3-position. In astrocytes, 3-O-glucuronides of the cis- and trans-resveratrol were only detected. The rat recombinant UGT1A6 and UGT2B1 isoforms were able to glucuronidate cis- and trans-resveratrol. Finally, in inflammatory conditions, trans-resveratrol glucuronidation was enhanced in astrocytes. CONCLUSION: Brain tissues are effective in the glucuronidation of resveratrol isomers. This metabolism pathway is likely to modulate the concentration of these biologically active substances.     

Rapid switch from intravenous epoprostenol to intravenous treprostinil in patients with pulmonary arterial hypertension

Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension (PAH); however, chemical instability and a short half-life have caused limitations in its use. The chemically stable prostacyclin analogue treprostinil has a longer half-life, and improves hemodynamics and signs/symptoms of PAH. This study investigated the feasibility of transitioning patients with PAH from intravenous epoprostenol to intravenous treprostinil using a rapid switch protocol. Twelve PAH patients were enrolled in a 12 week prospective open label study. Patients were switched from intravenous epoprostenol to intravenous treprostinil (1:1 ng/kg/min) by a direct switch of the medication reservoir from epoprostenol to treprostinil. The dose of treprostinil was adjusted throughout the study to achieve a 2-fold increase of treprostinil compared with the baseline epoprostenol dose. Rapid transition to treprostinil was achieved without serious adverse events and, baseline clinical status was maintained over 12 weeks. The mean baseline epoprostenol dose was 28 +/- 14 ng/kg/min. At week 12, the mean treprostinil dose was 62 +/- 30 ng/kg/min. All patients reported less prostacyclin-related side effects with treprostinil and remained on treprostinil after study completion. Selected patients with PAH can be safely transitioned from intravenous epoprostenol to intravenous treprostinil using a rapid switch protocol.     

Minocycline-induced cutaneous polyarteritis nodosa with antineutrophil cytoplasmic antibodies

Minocycline is an antibiotic widely used in the treatment of acne. Among the induced auto-immune disorders, cutaneous polyarteritis nodosa (PAN) is very rare. A new case is reported below. A 23-year-old female patient treated with minocycline for acne for 24 months developed sub-cutaneous nodules, livedo reticularis and pigmented lesions of the lower limbs. Antineutrophil cytoplasmic antibodies (ANCA) were positive at 1/320. Skin biopsy showed vasculitis of a medium-sized artery. The role of minocycline was suspected using the imputability criteria. The diagnosis of minocycline-induced cutaneous PAN with ANCA was sustained. After withdrawal of the treatment, the nodular lesions decreased spontaneously, whereas livedo disappeared and inflammatory parameters were normalized after oral corticosteroid therapy. Minocycline is a tetracycline which is efficient for treating acne. Auto-immune disorders are frequently observed. Among them, it is very rare to observe cutaneous PAN associated with positive ANCA. The pathophysiological mechanisms are discussed.     

Use of anti-collagenase properties of doxycycline in treatment of alpha 1-antitrypsin deficiency panniculitis.

Three patients (a 71-year-old man and 2 women, 73 and 50 years, respectively) with recurrent panniculitis associated with alpha 1-antitrypsin deficiency are presented. Because the concept of chronic and exaggerated inflammatory response in the patients with alpha 1-antitrypsin deficiency is based on the theory of protease-antiprotease imbalance, we suggest that tetracyclines will alleviate this condition. Indeed, tetracyclines were found to inhibit collagenase activity. The total remission of the condition in these 3 patients underlines for the first time the effects of doxycycline on a condition characterized by deficiency of the antiprotease system. A review of the 23 reported cases of panniculitis associated with alpha 1-antitrypsin deficiency is presented in table form.     

Intensive insulin therapy in the critically ill geriatric patient

Tight glucose control can significantly improve outcomes of critically ill geriatric patients in the critical care unit (CCU). In the past, blood glucose levels were managed by a point-of-care testing every 4 to 6 hours and using a sliding scale of insulin therapy. This article explores the need for more intensive intravenous insulin therapies. Studies have shown that patient outcomes improve by having a specific set of standing orders, a well-defined algorithm, and empowering the CCU nurses with these tools. Methods for initiating intensive intravenous insulin therapies are discussed along with some of the biggest challenges faced by CCU nurses at the bedside.     

Dysphagia in the elderly

The capacity to swallow or eat is a basic human need and can be a great pleasure. Older adults look forward to sharing mealtimes and participating in social interactions. The loss of capacity to swallow and dine can have far-reaching implications. With age, the ability to swallow undergoes changes that increase the risk for disordered swallowing, with devastating health implications for older adults. With the growth in the aging population, dysphagia is becoming a national health care burden and concern. Upward of 40% of people in institutionalized settings are dysphagic. There is a need to address dysphagia in ambulatory, acute care, and long-term care settings.     

Genital squamous cell carcinoma in men treated by photochemotherapy. A cancer registry-based study from 1978 to 1998

BACKGROUND: One single report from the U.S. 16-centre-trial indicated that psoralen and ultraviolet A radiation (PUVA) therapy may induce an increased risk of genital tumours in men, and protection of the genital area is, therefore, recommended. OBJECTIVES: To evaluate the relevance of this risk in routine clinical practice. METHODS: Two groups of patients were included in a 1978-98 retrospective study. Case records of men with genital squamous cell carcinoma (SCC) identified from the Cancer Registry of the Doubs area of France were examined for a history of PUVA therapy, topical tar treatment, psoriasis, human papillomavirus infection or genital dermatitis. In addition, all the dermatologists of the Doubs area (in public and private practice) using PUVA therapy were asked to provide information on the number of patients having received PUVA therapy and whether the genital area was exposed during treatment. RESULTS: Between 1978 and 1998, among the 48 men who had developed a genital SCC in the Doubs area, only one had a history of intensive PUVA therapy. About 150,000 treatments with PUVA therapy had been performed by 15 dermatologists in the Doubs area for 5400 patients since 1978. No case of genital SCC had been reported, despite the fact that the genital area had not been protected during UVA exposure. CONCLUSIONS: Although retrospective, our study demonstrates that the occurrence of genital SCC in men treated with PUVA therapy is a very rare event in common dermatological practice.     

A More Explicit Grading Scale Decreases Grade Inflation in a Clinical Clerkship

Objectives: The medical education literature contains few publications about the phenomenon of grade inflation. The authors' clinical clerkship grading scale suffered from apparent inflation relative to the recommended university distribution. The investigators hypothesized that a simple change of the shift grading cards, using explicit criteria, would decrease this grade inflation and aid to redistribute the shift evaluations.
Methods: This was a before-and-after study examining medical student shift evaluation grades. Evaluators and students were blinded to the purpose of the card change and were unaware that a study was being conducted. Beginning June 1, 2005, the authors altered the shift evaluation cards from the previous four choices of honors, high pass, pass, or fail to five choices of upper 5%, upper 25%, expected, below expected, or far below expected, and explicit grading criteria were provided. No other interventions to alter the grade distribution occurred. Data were collected on all evaluations from June 1, 2004, to March 31, 2005 (before change), and compared with data on all evaluations from June 1, 2005, to March 31, 2006 (after change).
Results: A total of 3,349 evaluations were analyzed: 1,612 before the card change and 1,737 after the change. The grade distribution before the card change was as follows: honors, 22.6%; high pass, 49.0%; pass, 28.4%; and fail, 0%. This compared with the following ratings after the card change: upper 5%, 9.8%; upper 25%, 41.2%; expected, 46.2%; below expected, 2.8%; and far below expected, 0% (p < 0.001).
Conclusions: A simple change in shift evaluation cards to include more explicit grading criteria resulted in a significant change in grade distribution and greatly decreased grade inflation.