Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

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Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

The radioprotector WR1065 reduces radiation-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells

N-(2-mercaptoethyl)-lt3-diaminopropane (WR1065) protects againstradiation-induced cell killing and mutagenesis at the hypoxanthine-guaninephosphoribosyl transferase (HGPRT) locus in V79 Chinese hamsterhing fibroblast cells. At a concentration of 4 mM, WR1065 wasfound to be effective in protecting against radiation-inducedcell lethality only if present during irradiation, e.g., a dosemodification factor (DMF) of 1.9. No protective effect was observedif the protector was added within 5 min after irradiation or3 h later, e.g., DMFs of 1.0 and 1.1, respectively. The effectof WR1065 on radiation-induced mutation, expressed as resistanceto the cytotoxic purine analogue 6-thioguanine (HGPRT), wasalso investigated. In contrast to the treatment-schedule dependencefor protection by WR1065 against cell killing, this agent waseffective in reducing radiation-induced mutations regardlessof when it was administered. Following a dose of 10 Gy of ⁶⁰Co-rays, the mutation frequencies observed per 10⁶ survivors were77 ± 8, 27 ± 6, 42 ± 7, and 42 ±7 for radiation only, and WR1065 present during, immediatelyafter, or 3 h after irradiation. These data suggest that althougha segment of radiation-induced damage leading to reproductivedeath cannot be modulated through the postirradiation actionof WR1065, processes leading to the fixation of gross geneticdamage and mutation induction in surviving cells can be effectivelyaltered and interfered with leading to a marked reduction inmutation frequency.     

Catheter obstruction during prolonged parenteral alimentation. Are lipids responsible?

Catheter obstruction is a serious incident during prolonged parenteral nutrition (PN). This retrospective study was carried out in order to compare the frequencies of catheter obstruction with nutritive mixtures in bags according to whether or not lipids were mixed with the entire 24 h nutritional supply (Group I, n=33) or infused separately (Group II, n=30). Our results show that obstructions are significantly more frequent in Group I (11 13 ) than in group 2 (3 10 ), appearing within a mean interval of 29 days after inserting the catheter. The global percentages of patients undergoing cyclic PN were the same in both patient groups. In group I, however, the percentage of patients on cyclic PN was significantly higher for the obstructed catheters (100%) than for the unobstructed catheters (59%). In conclusion, the mixture of lipids with the remainder of the nutrients in the conditions of this study is the prime cause of catheter obstruction, although the exact mechanism is not elucidated. The role of cyclic PN appears to be accessory.     

The influence of molecular structure on the affinity and efficacy of some β-adrenoceptor agonists

Summary The affinity and efficacy of a number of sympathomimetic amines structurally related to prenalterol and the selective ₁-adrenoceptor agonist RO 363 were determined using a combination of radioligand binding and organ bath techniques. Affinity of the molecules (pK _D) was calculated from their ability to displace the radioligand [¹²⁵I]iodocyanopindolol ([¹²⁵I]CYP) from -adrenoceptor sites in left atrial (₁) and uterine (₂) membrane homogenates. These pK _D values were used to calculate efficacy from the positive inotropic and uterine relaxant responses elicited by the drugs in organ bath experiments. The drugs studied were either arylethanolamines i.e., (–)-isoprenaline (ISO), p-hydroxyisoprenaline (pOH-ISO), compounds XIV and XVI or aryloxypropanolamine-derivatives, i.e., oxymethylene-isoprenaline (OM-ISO), prenalterol and Compound XI which possessed ap-phenol or catechol ring and an isopropyl or a homoveratryl amine substituent. Only ISO, OM-ISO, pOH-ISO and Compound XVI were active as agonists in both tissue preparations. These drugs were partial agonists which exhibited a wide range of pD₂ values and did not display any marked selectivity for either -adrenoceptor subtype. Compound XI and prenalterol were inactive as agonists and together with the partial agonists behaved as competitive antagonists to ISO in the two preparations. All drugs tested displaced [¹²⁵I]CYP from -adrenoceptor sites, however, there was also a wide range of potency amongst the drugs.Analysis of the structure-affinity and structure-efficacy relationships indicated that removal of the 3-hydroxyl group from the catechol ring reduces both affinity and efficacy without altering the selectivity of the drug for either -adrenoceptor subtype. While aryloxypropanolamine derivatives have generally higher affinities than arylethanol-amines, especially at -adrenoceptor sites, their efficacies are generally reduced at both -adrenoceptors. The presence of a homoveratryl group in aryloxypropanolamines enhances slightly the affinity for ₁- and reduces affinity for ₂-adrenoceptors. With this amine group, efficacy is markedly reduced at ₂- as opposed to ₂-adrenoceptor sites.Thus for prenalterol, the small degree of cardioselectivity can be attributed to the oxymethylene group whilst its lack of agonist activity (i.e., efficacy) reflects a combined action of this group and the absence of the 3-hydroxyl group on the phenyl ring. In RO363 it can be deduced that the oxymethylene group, together with the homoveratryl substituent are responsible for the observed selective affinity of the drug for ₁- as opposed to ₂-adrenoceptors.     

Man-in-the-barrel syndrome

In a prospective study of 34 comatose patients who had an episode of systemic hypotension, 11 had the "man-in-the-barrel" syndrome (MIB). They moved both legs spontaneously or in response to pain, but did not move either arm. One of 11 patients (9%) with MIB survived to leave the hospital; 8 of the 23 patients (35%) without MIB recovered. Of patients who moved at least one limb to pain and had intact pupillary, corneal, and oculocephalic reflexes 24 hours after insult, one of nine (11%) patients with MIB survived, compared with six of nine patients (67%) without MIB. MIB is common after cerebral hypoperfusion and carries a poor prognosis.     

Long-term efficacy of pergolide in patients with Parkinson's disease

We report the clinical course of 35 patients with Parkinson's disease who experienced an initially favorable response to pergolide and who were taking the drug for at least 6 months. The duration of pergolide treatment was 6-50 (25 +/- 16 SD) months. Of the 14 patients who remained on pergolide for over 2 years, 12 remained less disabled for 26 +/- 17 SD months, seven enjoyed increased "on" time for 39 +/- 8 SD months, and nine had a lower Hoehn-Yahr stage for 25 +/- 17 SD months. Pergolide was discontinued after 5-39 months in eight patients; six patients then deteriorated. Pergolide can remain efficacious in the treatment of Parkinson's disease for up to 50 months.     

Antegrade Colonic Lavage in Acute Colonic Obstruction

Conventional management of acute left sided colonic obstruction employs some form of proximal colostomy. Intraoperative antegrade colonic irrigation relieves proximal faecal loading and may permit safer primary resection and anastomosis. The results of a pilot study are presented, and are shown to be favourable.

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Trends in Vitamin C Consumption in the United States: 1999–2018

Low intakes of fruits and vegetables have resulted in suboptimal intakes of several micronutrients, including vitamin C. This cross-sectional study used data from 84,902 children/adults (≥1 y) who completed a 24-h dietary recall as part of the United States National Health and Nutrition Examination Survey (1999–2018). Mean vitamin C intakes from foods/beverages were calculated as were trends in major food/beverage sources of vitamin C. Percentages below the Estimated Average Requirement (EAR) were estimated. Overall, mean vitamin C consumption declined by 23% (97–75 mg/d; p-value for trend < 0.001). 100% fruit juice was the leading source of vitamin C (25.6% of total or 21.7mg/d), but this declined by 48% (25–13 mg/d; p-value for trend < 0.001). Whole fruit increased among children/adolescents (+75.8%;10–17 mg/d; p-value for trend < 0.001), but not adults, while the vegetable contribution was generally unchanged. The proportion of the population below the EAR increased by 23.8% on a relative scale or 9 percentage points on an absolute scale (38.3–47.4%). Declines in vitamin C intake is driven largely by decreases in fruit juice coupled with modest increases in whole fruit. Due to associations between vitamin C intake and numerous health outcomes these trends warrant careful monitoring moving forward.