Milacemide increases 5-hydroxytryptamine and dopamine levels in rat brain--possible mechanisms of milacemide antimyoclonic property in the p,p'-DDT-induced myoclonus

Milacemide, a glycine prodrug that is able to enter the brain readily, has been shown to have an antimyoclonic property in the p,p'-DDT-induced myoclonus syndrome. Milacemide increased regional 5-HT and dopamine and decreased 5-HIAA, DOPAC and HVA levels in naive rats. In p,p'-DDT-treated rats, 5-HT levels were unchanged at the time the rats experienced spontaneous myoclonus in all brain regions except in the striatum, where it increased. 5-HIAA levels increased but did not reach significant levels except in the striatum. Dopamine, DOPAC, HVA and norepinephrine were unchanged. When rats were treated concurrently with both p,p'-DDT and milacemide, regional 5-HT levels were increased and NE levels in the brainstem and cerebellum decreased. Depletion of brain serotonin by pretreatment with PCPA or with 5,7-DHT, or blocking 5-HT receptors with different 5-HT antagonists, failed to eliminate the antimyoclonic property of milacemide. This antimyoclonic effect of milacemide may be mediated through other mechanisms besides its ability to increase brain 5-HT levels. Possible mechanisms to be considered are its antiepileptic property, and its ability to increase brain glycine levels. Milacemide may have potential for therapeutic trials in patients with myoclonus.     

Synthesis of 3H, 14C and 2H4 labelled SCH 211803

[³H]SCH 211803, at a specific activity of 1.56 Ci/mmol, was prepared by direct exchange with tritiated water and platinum metal. [²H₄]SCH 211803 was prepared from [²H]formaldehyde in a seven step synthesis in 10% yield. [¹⁴C]SCH 211803 was prepared from N‐benzyl‐4‐hydroxy[2‐¹⁴C]piperidine in a four‐step synthesis in 35% radiochemical yield. Additionally a high specific activity batch of [³H]SCH 211803 was prepared by Ru(Ph₃P)₃Cl₂ catalysed exchange with 90 at% tritiated water to a specific activity of 35 Ci/mmol. Copyright © 2007 John Wiley & Sons, Ltd.     

Elective cholecystectomy with and without subhepatic drainage. A controlled, prospective study]

Based on the data of 56 patients undergoing elective cholecystectomy the value of subhepatic drainage is evaluated in a randomized controlled clinical trial. The design of the study and the perioperative management of the patients are described in detail and the results analyzed according to clinical course, blood tests and abdominal ultrasound.     

Diagnosing influenza: the value of clinical clues and laboratory tests.

OBJECTIVE: Our goal was to determine the utility of clinical clues, white blood cell (WBC) and differential counts, and a rapid antigen test for differentiating influenza from coexistent infectious diseases during influenza epidemics. STUDY DESIGN: Data were collected during 3 consecutive influenza outbreaks over a 2-year period. The information collected included date of onset, symptoms, vaccine status, WBC and differential counts, ZstatFlu test (ZymeTx, Oklahoma City, Ok), and influenza culture. Using culture positivity as the criterion for influenza diagnosis, we compared cases with noncases on each variable independently and by logistic regression. Receiver operating characteristic curves were plotted for WBC count, ZstatFlu, and their combination in an effort to determine the most useful diagnostic strategy. POPULATION: We included consecutive patients presenting to a family practice office with fever, cough, sore throat, myalgia, and/or headache during flu season. OUTCOMES MEASURED: The outcomes were sensitivity, specificity, and other measures of test accuracy. RESULTS: Culture-positive cases could not be reliably distinguished from those that were culture negative using symptoms or vaccination status. Both WBC count and ZstatFlu results discriminated fairly well, and their combination did somewhat better. Differential counts were not helpful. WBC counts above 8000 were associated with a low probability of influenza. The sensitivity and specificity of the ZstatFlu were 65% and 83%, respectively. CONCLUSIONS: Our data suggest that symptoms and vaccine status do not reliably identify patients with influenza. Use of WBC counts and the ZstatFlu test can be helpful. The sequence, combination, and criteria for use of these tests depend on tradeoffs between undertreatment of influenza cases and the overtreatment of noninfluenza cases, and the cost and benefit projections for individual patients.     

The role of platelet-activating factor in human fetal lung maturation

The presence of the potent bioactive glycerophospholipid 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) in a lamellar body-enriched fraction of amniotic fluid from women in labor has prompted the present investigation to examine the fetal lung as the possible tissue source of this platelet-activating factor. The metabolism of platelet-activating factor was assessed in an organ culture system in which human fetal lung tissue (12 to 16 weeks) was incubated for 6 to 7 days. During this period, the type II pneumonocytes differentiate and surfactant glycerophospholipid biosynthesis is greatly enhanced. The initial specific activity of the platelet-activating factor biosynthetic enzyme lyso-platelet-activating factor:acetyl-coenzyme A acetyltransferase is two to three times greater in microsomes prepared from fetal lung than in those from the fetal liver or kidney. The specific activity of acetyltransferase in lung tissue increased twofold after 6 days in organ culture. A similar increase in acetyltransferase activity was found in the lamellar body-enriched (18,000 X g) subcellular fraction of fetal lung. The activity of the major platelet-activating factor-inactivating enzyme platelet-activating factor acetylhydrolase did not change significantly in the lung explants during the incubation period. Associated with the enhanced platelet-activating factor biosynthetic activity in the fetal lung was an increase in the platelet-activating factor concentration, from 17 to 37 fmol/mg of protein between days 0 and 6 of culture. Corresponding increases of 3.3- and 3.8-fold in the concentrations of the platelet-activating factor lipid precursors lyso-platelet-activating factor and the 2-acyl congener were found after 6 days in culture. A reciprocal relationship was found between platelet-activating factor and glycogen content as the lung tissue matured in vitro; specifically, as the platelet-activating factor level increased, glycogen decreased from 340 to 77 micrograms/mg of protein. We suggest that platelet-activating factor may mediate the onset of glycogenolysis in fetal lung tissue similar to that in the isolated, perfused rat liver (Shukla SD, Buxton DB, Olson MS, Hanahan DJ. Acetylglyceryl ether phosphorylcholine. A potent activator of hepatic phosphoinositide metabolism and glycogenolysis. J Biol Chem 1983; 258:10212-4). The increased rate of glycogen degradation may serve as the carbon and energy source for the increased synthesis of glycerophospholipids required for surfactant production.(ABSTRACT TRUNCATED AT 400 WORDS)     

INSL3 has tumor‐promoting activity in thyroid cancer

The functional role of INSL3 and its receptor RXFP2 in carcinogenesis is largely unknown. We have previously demonstrated (pro‐)cathepsin‐L as a target of INSL3 in human thyroid cancer cells facilitating penetration of tumor cells through elastin matrices. We demonstrate the expression of RXFP2 in human thyroid tissues and in mouse follicular thyroid epithelial cells using Cre‐recombinase transgene driven by Rxfp2 promoter. Recombinant and secreted INSL3 increased the motility of thyroid carcinoma (TC) cells in an autocrine/paracrine manner. This effect required the presence of RXFP2. We identified S100A4 as a novel INSL3 target molecule and showed that S100A4 facilitated INSL3‐induced enhanced motility. Stable transfectants of the human follicular TC cell line FTC‐133 expressing and secreting bioactive human INSL3 displayed enhanced anchorage‐independent growth in soft agar assays. Xenotransplant experiments in nude mice showed that INSL3, but not EGFP‐mock transfectants, developed fast‐growing and highly vascularized xenografts. We used human umbilical vein endothelial cells in capillary tube formation assays to demonstrate increased 2‐dimensional tube formations induced by recombinant human INSL3 and human S100A4 comparable to the effect of vascular endothelial growth factor used as positive control. We conclude that INSL3 is a powerful and multifunctional promoter of tumor growth and angiogenesis in human thyroid cancer cell xenografts. INSL3 actions involve RXFP2 activation and the secretion of S100A4 and (pro‐)cathepsin‐L.     

Florid reactive periostitis

A case of florid reactive periostitis of the thumb is reported. This rare, benign, bone-producing lesion is easily confused with osteosarcoma. It is also known as parosteal or nodular fascitis. Careful histologic and radiographic evaluations are needed to establish the diagnosis and avoid unnecessary amputation. Marginal excision seems to be adequate treatment.     

The influence of culture on immigrant women's mental health care experiences from the perspectives of health care providers

It is well documented that serious mental health problems such as depression, schizophrenia, and post migration stress disorders exist among immigrant women. Informed by Kleinman's explanatory model, this qualitative exploratory study was conducted with seven health care providers who provided mental health services to immigrant women. Analysis of the data revealed that (a) immigrant women face many difficulties when accessing mental health care services due to cultural differences, social stigma, and unfamiliarity with Western biomedicine, (b) spiritual beliefs and practices that influence immigrant women's mental health care practices, and (c) the health care provider-client relationship, which exerts great influence on how immigrant women seek mental health care. The study also revealed that cultural background exerts both positive and negative influences on how immigrant women seek mental health care. We suggest that although cultural knowledge and practices influence immigrant women's coping choices and strategies, awareness of social and economic differences among diverse groups of immigrant women is necessary to improve the accessibility of mental health care for immigrant women.