Dynamic pressure–flow relationship of the cerebral circulation during acute increase in arterial pressure

The physiological mechanism(s) for the regulation of the dynamic pressure–flow relationship of the cerebral circulation are not well understood. We studied the effects of acute cerebral vasoconstriction on the transfer function between spontaneous changes in blood pressure (BP) and cerebral blood flow velocity (CBFV) in 13 healthy subjects (30 ± 7 years). CBFV was measured in the middle cerebral artery using transcranial Doppler. BP was increased stepwise with phenylephrine infusion at 0.5, 1.0 and 2.0 μg kg^–1 min^–1. Phenylephrine increased BP by 11, 23 and 37% from baseline, while CBFV increased (11%) only with the highest increase in BP. Cerebrovascular resistance index (BP/CBFV) increased progressively by 6, 17 and 23%, demonstrating effective steady-state autoregulation. Transfer function gain at the low frequencies (LF, 0.07–0.20 Hz) was reduced by 15, 14 and 14%, while the phase was reduced by 10, 17 and 31%. A similar trend of changes was observed at the high frequencies (HF, 0.20–0.35 Hz), but gain and phase remained unchanged at the very low frequencies (VLF, 0.02–0.07 Hz). Windkessel model simulation suggests that increases in steady-state cerebrovascular resistance and/or decreases in vascular compliance during cerebral vasoconstriction contribute to the changes in gain and phase. These findings suggest that changes in steady-state cerebrovascular resistance and/or vascular compliance modulate the dynamic pressure–flow relationship at the low and high frequencies, while dynamic autoregulation is likely to be dominant at the very low frequencies. Thus, oscillations in CBFV are modulated not only by dynamic autoregulation, but also by changes in steady-state cerebrovascular resistance and/or vascular compliance.     

Hepatic insulin resistance,metabolic syndrome and cardiovascular disease

BackgroundThe metabolic syndrome is a constellation of common metabolic disorders that is associated with cardiovascular disease. Insulin resistance has a central role in the pathophysiology of metabolic syndrome.Recent advancesIt is now commonly accepted that chronic inflammation associated with visceral obesity induces insulin resistance in the liver. Chronic inflammation is characterized by the production of abnormal adipokines and cytokines such as TNF-α, FFA, IL-1, IL-6, leptin and resistin. These factors inhibit insulin signalling in hepatocytes by activating SOCS proteins, several kinases such as JNK, IKK-β and PKC and protein tyrosine phosphatases such as PTP1B and PTEN, that in turn impair insulin signalling at insulin receptor and insulin receptor substrate (IRS) level. Hepatic insulin resistance in turn causes impaired suppression of glucose production by insulin in hepatocytes leading to hyperglycemia. An important and early complication of hepatic insulin resistance is the induction of hepatic VLDL production, via changes in the rate of apoB synthesis and degradation and de novo lipogenesis, or increased FFA flux from adipose tissue into the liver. Insulin resistance also stimulates the production of CRP and PAI-1, both markers of an inflammatory state. All metabolic abnormalities related to hepatic insulin resistance have been shown to directly or indirectly promote atherosclerosis. Hyperglycemia induces a series of alterations including endothelial dysfunction, cellular proliferation, changes in extracellular matrix conformation and impairment of LDL receptor-mediated uptake decreasing the in vivo clearance of LDL. Small dense LDLs associated with high circulating VLDL have higher affinity to the intimal proteoglycans leading to the penetration of more LDL particles into the arterial wall. CRP can also accelerate atherosclerosis by increasing the expression of PAI-1 and adhesion molecules in endothelial cells, inhibition of nitric oxide formation and increasing LDL uptake into macrophages.ConclusionsOverall, growing evidence suggests that hepatic insulin resistance is sufficient to induce several components of the metabolic syndrome and promote progression to cardiovascular disease. Many unresolved questions remain however on the molecular and cellular mechanisms that trigger hepatic insulin resistance and promote the development of clinical metabolic syndrome.     

Corneal interface contamination during laser in situ keratomileusis

PURPOSE: To measure the rate of corneal interface contamination during laser in situ keratomileusis (LASIK), determine probable sources of the contamination, and evaluate how the cornea reacts to the contamination. SETTING: Department of Ophthalmology, Baqyatallah Hospital, Baqyatallah University, Tehran, Iran. METHODS: In this case series, 200 eyes were evaluated for the corneal interface contamination at the end of LASIK. Cultures were taken from the upper and lower eyelid margins and the inferior fornices before surgery and from the corneal interface and the instrument at the end of surgery. Media were cultured at 37 degrees C for 14 days under aerobic and anaerobic conditions. Bacteria from positive cultures were isolated and identified by biochemical procedures to determine the species of the organisms. RESULTS: The rate of contamination was 24.5%. The most common retrieved organism was Staphylococcus epidermidis (43 cases, 87.7%). None of the contaminated or noncontaminated cases developed corneal ulcers; however, 2 eyes developed diffuse lamellar keratitis. CONCLUSION: The corneal stroma has the ability to clear introduced microorganisms during LASIK.     

NOSH-Aspirin: A Novel Nitric Oxide-Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals

A series of new hybrids of aspirin (ASA), bearing both nitric oxide (NO) and hydrogen sulfide (H(2)S)-releasing moieties were synthesized and designated as NOSH compounds (1-4). NOSH-1 (4-(3-thioxo-3H-1,2-dithiol-5-yl) phenyl 2-((4-(nitrooxy)-butanoyl)oxy) benzoate); NOSH-2 (4-(nitrooxy)butyl (2-((4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)carbonyl)phenyl)); NOSH-3 (4-carbamothioylphenyl 2-((4-(nitrooxy)butanoyl)-oxy)benzoate); and NOSH-4 (4-(nitrooxy)butyl 2-(5-((R)-1,2-dithiolan-3-yl)pentanoyloxy)-benzoate). The cell growth inhibitory properties of compounds 1-4 were evaluated in eleven different human cancer cell lines of six different tissue origins. These cell lines are of adenomatous (colon, pancreatic, lung, prostate), epithelial (breast), and lymphocytic (leukemia) origin. All NOSH compounds were extremely effective in inhibiting the growth of these cell lines. NOSH-1 was the most potent, with an IC(50) of 48 ± 3 nM in HT-29 colon cancer cells. This is the first NSAID-based compound with such potency. This compound was also devoid of any cellular toxicity, as determined by LDH release. NOSH-1 was comparable to aspirin in its anti-inflammatory properties, using the carrageenan rat paw edema model.     

MyoRing植入术治疗圆锥角膜的疗效观察

目的：比较MyoRing植入前后圆锥角膜(KCN)患者角膜前后表面散光和全屈光散光。

方法：历史队列研究。比较植入360度全环植入物(MyoRing)的KCN患者的术前和术后全屈光、角膜前后表面散光,术后3、6、9、12 mo连续随访四次。

结果：共纳入KCN患者79例85眼,其中男43例,女36例,平均年龄29±7.41(17-48)岁。随访期间,全屈光散光、角膜前后表面散光呈减少趋势。MyoRing植入后12 mo,总屈光散光测量值显著下降2.09 D(4.27±3.15 vs 2.18±1.63 D,P<0.001)。此外,术后测量显示,角膜前表面和后表面散光分别改善约3.20 D和0.59 D\〖6.40±1.90 vs 3.20±1.75 D(P<0.001)和1.30±0.55 vs 0.71±0.35(P<0.001)\〗

结论：MyoRing植入可显著改善散光参数,包括全屈光散光以及角膜前后表面散光。