Synthesis, chemical, and biological properties of vinylogous hydroxamic acids: dual inhibitors of 5-lipoxygenase and IL-1 biosynthesis.

Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.     

Hormone Responses to an Acute Bout of Low Intensity Blood Flow Restricted Resistance Exercise in College-Aged Females

The purpose of this study was to determine whether the acute hormone response to exercise differed between low intensity blood flow restricted resistance exercise and traditional high-intensity resistance exercise in college-aged women. A total of 13 healthy women (aged 18-25 yrs), who were taking oral contraceptives, volunteered for this randomized crossover study. Subjects performed a session of low intensity blood flow restricted resistance exercise (BFR) (20% of 1-RM, 1 set 30 reps, 2 sets 15 reps) and a session of traditional high intensity resistance exercise without blood flow restriction (HI) (3 sets of 10 repetitions at 80% of 1-RM) on separate days. Fasting serum cortisol and growth hormone (GH) and blood lactate responses were measured in the morning pre and post exercise sessions. GH (Change: HI: 6.34 ± 1.72; BFR: 4.22 ± 1.40 ng·mL^-1) and cortisol (Change: HI: 4.46 ± 1.53; BFR: 8.10 ± 2.30 ug·dL^-1) significantly (p < 0.05) increased immediately post exercise for both protocols compared to baseline and there were no significant differences between the protocols for these responses. In contrast, blood lactate levels (HI: 7.35 ± 0.45; BFR: 4.02 ± 0.33 mmol·L^-1) and ratings of perceived exertion were significantly (p < 0.01) higher for the HI protocol. In conclusion, acute BFR restricted resistance exercise stimulated similar increases in anabolic and catabolic hormone responses in young women.

Key Points

• Growth hormone and cortisol levels significantly increased after a single bout of low intensity blood flow restricted resistance exercise in young women.
• There were no significant differences in hormone responses between the low intensity blood flow restricted protocol and the traditional high intensity higher total workload protocol.
• Low intensity blood flow restricted resistance exercise provides a sufficient stimulus to elicit anabolic and catabolic hormone responses in young women.

Key Words: Growth Hormone, Cortisol, blood flow restriction     

Young red blood cells; observations about the cytometric and morphologic alterations in the beginning of their life

Summary A recently described separation technique consisting of a combination of counterflow centrifugation and subsequent density (Percoll) scparation was tested for its ability to enrich red cell populations with young cells in comparison to either separation technique alone. The relative age of every fraction was determined by HbAlc measurements, resulting in the lowest HbAlc for the combination method. Conventional reticulocyte counting and floweytometric counting with thiazole orange indicated that in the youngest fractions the combination method showed the highest reticulocyte counts. There was a good correlation between manual and flowcytometric counting results. Radio-iron studies showed a two-fold enrichment with young cells in the fraction with the lowest HbAIc acquired by the combination technique in comparison to the other two methods. Cytometric measurements showed that the fractions with the lowest HbAlc were the ones with the highest MCV and MCH and the lowest MCHC. Besides loss of their RNA-material, young cells already seem to loose water and haemoglobin like older cells, resulting in a decrease of MCV and MCH and in increase in MCHC. It is concluded that combining counterflow centrifugation with subsequent density fractionation results in superior enrichment with young cells in comparison to the results of each method alone.     

Transvenous Biopsy in the Diagnosis of Intravascular or Perivascular Neoplasm: A Single-Center Retrospective Analysis of 36 Patients

Between September 2008 and August 2017, 36 patients (mean age 56 y; range, 30–89 y) underwent transvenous biopsy of suspected tumor thrombus or perivascular tumor. Intravascular biopsy was pursued because of inaccessible percutaneous access in 9 patients (25%) and as part of a planned revascularization procedure in 27 patients (75%). Histopathologic results showed malignancy in 26 patients (72%) and benign etiologies in 10 patients (28%). No patients required repeat biopsy. There were no complications related to the biopsy procedure. The present series suggests that transvenous biopsy is a safe and accurate method of intravascular and perivascular mass tissue sampling.     

Coincidence of patchy inputs from the lateral geniculate complex and area 17 to the cat's Clare-Bishop area

Pathways from a variety of structures to the largest of the cat's suprasylvian visual areas, the Clare-Bishop area, were found to patchy. These inputs arose from the lateral geniculate complex, from area 18, from area 19, and, as noted by Montero (Brain Behav. Evol. 18:194-218, '81), from area 17. The Clare-Bishop area was previously delineated on the basis of its uniform pattern of connections with cortex and thalamus (Sherk: J. Comp. Neurol. 247:1-31, '86) and found to incorporate pieces of several retinotopically defined areas (Tusa, Palmer, Rosenquist: Cortical Sensory Organization. Vol 2. Multiple Visual Areas. Clifton, NJ: Humana Press, pp. 1-31, '81). However, since individual patches did not correspond to particular retinotopically defined areas, other explanations of afferent patchiness were sought. An obvious question is whether the patches originating from different sources are systematically related to each other. Two hypotheses were considered. First, different inputs--for example, from the lateral geniculate nucleus (LGN) and from area 17--might terminate in intermingled but mutually exclusive zones in the Clare-Bishop area. Second, multiple patches of input might reflect duplicate representations of the corresponding visual field segment in the Clare-Bishop area. Both hypotheses were tested by injecting the lateral geniculate complex and either area 17 or area 19 with different anterograde tracers. In each case the two injections involved regions of the visual field that coincided to some degree, ranging from near-total overlap to almost complete exclusion. The first hypothesis predicted that the different labels in the Clare-Bishop area would never be found to overlap, while the second hypothesis predicted that when injections were closely matched retinotopically, there would be extensive overlap between patches. The results supported the second hypothesis: the better the retinotopic match between injections, the greater the overlap found between labeled geniculate and cortical input in the Clare-Bishop area. However, the multiplicity of patches seen in some experiments, and the close spacing between some patches, suggested that an additional, nonretinotopic mechanism also contributes to patchiness in the projections to the Clare-Bishop area.     

Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.     

308 nm Excimer laser ablation of cartilage

This article reports the investigation of the XeCl excimer laser as a cutting-ablating tool for human fibrocartilage and hyaline cartilage. Quantitative measurements were made of tissue ablation rates as a function of fluence in meniscal fibrocartilage and articular hyaline cartilage. A force of 1.47 Newtons was applied to an 800-μm fiber with the laser delivering a range of fluences (40-190 mJ/mm²) firing at a frequency of 5 Hz. To assess the effect of repetition rate on depth per pulse, a set of measurements was made at a constant fluence of 60 mJ/mm², with the repetition rate varying from 10 to 40 Hz. Histologic and morphometric analysis of preserved specimens was performed using light microscopy. The results of these studies revealed that the ablation rate was directly proportional to fluence over the range tested. Fibrocartilage was ablated at a rate 2.56 times faster than hyaline cartilage. Repetition rate had no effect on the penetration per pulse. Adjacent tissue damage was noted to be minimal (10–70 μm). The excimer laser achieved ablation rates adequate for arthroscopic applications. © 1994 Wiley-Liss, Inc.