Prolonged vitamin C supplementation and recovery from eccentric exercise

We have previously shown that vitamin C supplementation affects recovery from an unaccustomed bout of demanding exercise, with the most pronounced effect being that on plasma interleukin-6 concentration. However, because of the proposed role of interleukin-6 in the regulation of metabolism, it was unclear whether this represented a reduced response to muscle damage or some form of interaction with the metabolic demands of the activity. Therefore, the aim of the present study was to investigate the effect of the same form of supplementation on a bout of exercise that initiated similar muscle damage but had a low metabolic cost. Fourteen male subjects were allocated to either a placebo (P) or a vitamin C (VC) group. The VC group consumed 200 mg of ascorbic acid twice a day for 14 days prior to a bout of exercise and for the 3 days after exercise. The P group consumed identical capsules that contained 200 mg lactose. Subjects performed 30 min of downhill running at a gradient of –18% and recovery was monitored for up to 3 days after exercise. Plasma VC concentrations in the VC group increased following supplementation. Nevertheless, downhill running provoked a similar increase in circulating markers of muscle damage (creatine kinase activity and myoglobin concentration) and muscle soreness in P and VC groups. Similarly, although downhill running increased plasma interleukin-6, there was no effect from VC supplementation. These results suggest that vitamin C supplementation does not affect interleukin-6 concentrations following eccentric exercise that has a low metabolic component.     

Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway

Werner Syndrome (WS) is characterized by premature aging, genomic instability, and cancer. The combined impact of WRN helicase deficiency and limiting telomere reserves is central to disease pathogenesis. Here, we report that cells doubly deficient for telomerase and WRN helicase show chromosomal aberrations and elevated recombination rates between telomeres of sister chromatids. Somatic reconstitution of WRN function, but not a WRN helicase-deficient mutant, abolished telomere sister chromatid exchange (T-SCE), indicating that WRN normally represses T-SCEs. Elevated T-SCE was associated with greater immortalization potential and resultant tumors maintained telomeres via the alternative lengthening of telomere (ALT) pathway. We propose that the increased incidence of chromosomal instability and cancer in WS relates in part to aberrant recombinations between sister chromatids at telomeres, which facilitates the activation of ALT and engenders cancer-relevant chromosomal aberrations and tumor formation.     

Strategies for greater impact in developing countries

Effective AIDS education programs are needed to prevent AIDS. They must integrate HIV/AIDS messages into basic health care services and adapted them to cultural norms and values. They should eliminate the mystery surrounding human sexuality. Effective AIDS education programs must examine control of communicable diseases and the relationship between gender issues and effective health care treatment. The infrastructure and resources to direct vertical HIV/AIDS programs generally do not exist in developing countries. All too often senior professionals accept positions in these vertical programs, which limits their ability to lobby for integrated HIV/AIDS programs. Donor organizations should make sure that all projects which they support have an AIDS component and work with other organizations to ensure that prevention and control of sexually transmitted diseases (STD)/HIV/AIDS is completely integrated into health care delivery services. All health workers should undergo AIDS prevention and control training. Supervisors should make sure that subordinates practice AIDS control. Benefit packages should not be offered to attract health workers. Just because nationals may make up an information, education, and communication (IEC) program does not mean that they will adapt the program to cultural values. Donors must provide appropriate educational strategies and programs to developing countries. Social change evolves from the culture. Health care workers must help find culturally appropriate education strategies. IEC has not reached its objectives in prevention and control of STDs. Communication mechanisms that allow human sexuality to be a subject of every day discussion without causing embarrassment, uneasiness, and outrage are needed.     

Glycosylation is not required for the fusion activity of the G protein of vesicular stomatitis virus in insect cells

The gene encoding the complete glycoprotein of vesicular stomatitis virus (VSV, Indiana serotype G protein) with potential asparagine-linked glycans at amino acid residues 179 and 338 was inserted into a baculovirus transfer vector pAcYM1, derived from the nuclear polyhedrosis virus of Autographa californica (AcNPV). The gene was placed under the control of the AcNPV polyhedrin promotor and expressed by the derived recombinant viruses to high levels in Spodoptera frugiperda cell lines. The principal product was the glycosylated version of the G protein, although some alternative (including probable degradation) forms of the protein were also observed. Similar recombinant viruses were prepared with deletion of one, the other, or both glycosylation sites of the VSV G protein. All forms expressed VSV G protein derivatives and mediated cell fusion and the production of syncytia at low pH. The fusogenic properties of the VSV G protein expressed on the surface of insect cells was prevented using anti-VSV sera, or by elevating the pH above 6.2. A reduction of the pH to 5.5, or 5.0, accelerated the rate of syncytia formation.     

Immunoglobulin M antibody capture enzyme-linked immunosorbent assay for diagnosis of St. Louis encephalitis

Sera from patients with St. Louis encephalitis were tested with an immunoglobulin M (IgM) antibody capture enzyme immunoassay (MAC ELISA). The assay used five reagents: antihuman IgM, test serum, sucrose-acetone-extracted mouse brain antigen, broadly cross-reactive flavivirus monoclonal antibody conjugated to alkaline phosphatase, and substrate (p-nitrophenyl phosphate). MAC ELISA endpoint titers correlated (r = 0.893) with the absorbance value of a 1:100 dilution of patient serum. Significant (fourfold or greater) changes in the endpoint titers between paired sera corresponded to a critical ratio (ratio of absorbance values at the 1:100 dilution) of greater than or equal to 1.3. IgM antibodies were detected in 71% of patients bled at 0 to 3 days after the onset of illness, in 99% bled at 4 to 21 days, and in 91% bled at 22 to 67 days. Thereafter, the IgM seropositivity rate declined; however, 29% of sera were still positive at 115 to 251 days after the onset of illness. MAC ELISA titers were significantly correlated with hemagglutination inhibition (r = 0.258) and neutralization (r = 0.711) titers. Because IgM antibodies appeared early and waned rapidly, a diagnosis was made on the basis of a decrease in titer more often by MAC ELISA than by hemagglutination inhibition, complement fixation, or neutralization tests. IgM antibodies generally showed a high degree of specificity; heterologous cross-reactions were, however, present in 4 of 14 sera examined. The MAC ELISA is useful for the rapid, early diagnosis of St. Louis encephalitis.     

Blood concentrations and clinical findings in nonfatal and fatal intoxications involving glutethimide and codeine

Blood concentrations and clinical findings were evaluated in twenty-six nonfatal and twelve fatal intoxications involving the combination of glutethimide and codeine ("loads"). The mean glutethimide concentration was 10 +/- 5 mg/L for nonfatal cases (range 2-18 mg/L) and 13.9 +/- 6.6 mg/L for fatal cases (range 4.6-26.4 mg/L). The mean codeine concentration for fatal intoxications was 1.21 +/- 1.17 mg/L (range 0.13-4.32 mg/L). Codeine concentrations were not measured in cases of nonfatal intoxication. Nine nonfatal cases required hospitalization on a medical ward (mean length of stay 3 +/- 3 days). Depressed level of consciousness was the most common abnormal physical finding (24 cases); 18 patients were lethargic but arousable with nonpainful stimulation and 6 patients with serum glutethimide concentrations of 10 mg/L or greater were comatose. The level of consciousness showed statistically significant correlation with the glutethimide concentration (P less than 0.01). Twenty-four nonfatal intoxications involved at least one other drug in addition to glutethimide and codeine (salicylates in 12 and acetaminophen in 4), while only 7 fatal cases involved at least one additional drug (acetaminophen and diazepam in 3 each). The finding of glutethimide should prompt a search for codeine and vice versa, especially when the presence of either does not in and of itself explain the clinical condition of the patient.     

The Ljubljana IUDS: further observations on surface morphology

Twelve IUDs that had been worn from 8 years 10 months to 24 years were examined by SEM. Photomicrographs of selected samples are shown, and a discussion of the nature of the surface encrustations is provided. The authors are of the opinion that surface encrustations are generic to different types of IUDs and that their clinical significance is presently unknown.

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Resumen Doce DIU que fueron usados de 8 años 10 meses a 24 años, se examinaron por microscopio de barrido. Se muestran microfotografías de especímenes seleccionados y se especula sobre la naturaleza de las incrustaciones en la superficie. Los autores son de opinión que las incrustaciones en la superficie son comunes para los distintos tipos de DIU y que actualmente se desconoce su significado clínico.

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Résumé Douze stérilets qui ont été utilisés pendant une période allant de 8 ans et 10 mois à 24 ans ont fait object 'dun examen sous microscope électronique. Des microphotographies de spécimens sélectionnés illustrent ce document. Après avoir examiné la nature des incrustations superficielles, les auterus en ont tiré la conclusion que les différents types de stérilets présentent tous les mêmes incrustations dont on ne connaît pas encore la signification clinique.

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Presented at the 3rd International Meeting of the Society for the Advancement of Contraception, Bordeaux, France, September, 1985     

Stability of cephapirin sodium admixtures after freezing and conventional or microwave thaw techniques

The freeze-microwave thaw technique has important advantages compared with conventional piggyback delivery systems. A requirement for the implementation of this technique, however, is the documentation of antibiotic stability following freezing and microwave thawing. The purpose of this study was to assess the stability of a commonly used cephalosporin, cephapirin sodium, following freezing and conventional or microwave thawing. This data was not previously available. Cephapirin sodium was admixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinylchloride minibags at concentrations of 10 and 40 mg/ml and then frozen for 14 days. Admixtures were then thawed conventionally or by microwave heating. Cephapirin concentrations were determined spectrophotometrically after reconstitution, immediately after thawing, and 6, 12, and 24 hours after thawing. No significant differences in admixture potency after reconstitution, immediately after thawing, or at 6, 12, and 24 hours after thawing were observed when thaw techniques were compared. All admixtures retained at least 90% of labeled content regardless of thaw technique, type of diluent, or initial concentration. In addition, all admixtures retained at least 90% potency 24 hours after thawing when compared with the actual concentration determined immediately after reconstitution. The rate of cephapirin degradation was not influenced by thaw technique, type of diluent, or initial admixture concentration. The results of this study suggest that cephapirin sodium may be added to the list of drugs capable of withstanding freeze-microwave thaw treatment.     

Milk-Fat Intake and Differences in Abdominal Adiposity and BMI: Evidence Based on 13,544 Randomly-Selected Adults

The primary purpose of this investigation was to evaluate the relationship between milk-fat intake and obesity, particularly abdominal obesity, in 13,544 U.S. adults. A lesser objective was to measure the degree to which the association was influenced by multiple potential confounding variables. This cross-sectional study used data from the 2011–2016 National Health and Nutrition Examination Survey (NHANES). Quantity of milk-fat regularly consumed was the exposure variable. Sagittal abdominal diameter (SAD), a measure of abdominal obesity, and body mass index (BMI) were the outcome variables. Sagittal abdominal diameter is a strong predictor of visceral abdominal fat, when measured by computed tomography, and has been shown to predict cardiometabolic disorders better than BMI. After controlling for age, race, gender, physical activity, leisure computer use and gaming, alcohol habits, and cigarette use, significantly lower BMIs were associated with consistent non-fat and full-fat milk consumption (F = 4.1, p = 0.0063). A significantly lower SAD was associated only with regular consumption of non-fat milk (F = 5.0, p = 0.0019). No significant differences were detected between the other milk-fat groups or milk abstainers. In this nationally representative sample, only 19.6% of adults regularly consumed low-fat milk. In conclusion, consistent non-fat milk intake was predictive of lower levels of abdominal adiposity compared to consumption of higher levels of milk-fat.     

Regulatory review time and pharmaceutical research and development

In the United States, all newly developed drugs undergo a lengthy review process conducted by the US Food and Drug Administration (FDA). These regulatory delays have direct immediate costs for drug manufacturers and patients waiting for treatment. Under certain market conditions, regulatory delays may also affect future research and development (R&D) strategies of pharmaceutical companies. To estimate the magnitude of this effect, we match data on drugs in the development pipeline in 2006 to data that we collect on FDA review times for all drugs approved between 1999 and 2005. Employing a rich and novel set of controls that affect drug R&D decisions and, potentially, regulatory review lags, we find that on average, three additional months of delay result in one fewer drug in development in that drug category. Our results suggest that the length of the regulatory delay matters for pharmaceutical firms' R&D decisions and that the firms are likely unable to pass on these costs onto consumers.