Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Coronary bypass in vascular patients: a relatively high-risk procedure

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.     

Characterization and electrochemical properties of CF4 plasma-treated boron-doped diamond surfaces

The effect of CF₄ plasma etching on diamond surfaces, with respect to treatment time, was investigated using scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and electrochemical measurements. SEM observations and Raman spectra indicated an increase in surface roughening on a scale of 10–20 nm, and an increase in crystal defect density was apparent with treatment time in the range of 10 s to 30 min. In contrast, alteration of the diamond surface terminations from oxygen to fluorine was found to be rather rapid, with saturation of the F/C atomic ratio estimated from XPS analysis after treatment durations of 1 min and more. The redox kinetics of Fe(CN)₆^3−/4− was also found to be significantly modified after 10 s of CF₄ plasma treatment. This behavior shows that C–F terminations predominantly affect the redox kinetics compared to the effect on the surface roughness and crystal defects. The double-layer capacitance (C_dl) of the electrolyte/CF₄ plasma-treated boron-doped diamond interface was found to show a minimum value at 1 min of treatment. These results indicate that a short-duration CF₄ plasma treatment is effective for the fabrication of fluorine-terminated diamond surfaces without undesirable surface damage.     

Pool boiling on a superhydrophilic surface

Titanium Dioxide, TiO₂, is a photocatalyst with a unique characteristic. A surface coated with TiO₂ exhibits an extremely high affinity for water when exposed to UV light and the contact angle decreases nearly to zero. Inversely, the contact angle increases when the surface is shielded from UV. This superhydrophilic nature gives a self-cleaning effect to the coated surface and has already been applied to some construction materials, car coatings and so on. We applied this property to the enhancement of boiling heat transfer. An experiment involving the pool boiling of pure water has been performed to make clear the effect of high wettability on heat transfer characteristics. The heat transfer surface is a vertical copper cylinder of 17 mm in diameter and the measurement has been done at saturated temperature and in a steady state. Both TiO₂-coated and non-coated surfaces were used for comparison. In the case of the TiO₂-coated surface, it is exposed to UV light for a few hours before experiment and it is found that the maximum heat flux (CHF) is about two times larger than that of the uncoated surface. The temperature at minimum heat flux (MHF) for the superhydrophilic surface is higher by 100 K than that for the normal one. The superhydrophilic surface can be an ideal heat transfer surface. Copyright © 2002 John Wiley & Sons, Ltd.     

Treatment of essential arterial hypertension with hypercholesterolemia. Effects of an alpha-adrenergic blocker and an inhibitor of the angiotensin converting enzyme

BACKGROUND: Hypertension and hypercholesterolemia are frequently associated with this leading to considerable cardiovascular risk. METHODS: An open parallel randomized study was performed in which the effects of doxazosin, an alpha-adrenergic blocker and enalapril, an inhibitor of the angiotensin converting enzyme were compared in 70 patients with essential high blood pressure and plasma cholesterol levels greater than 240 mg/dl. Following 2-4 weeks of placebo administration the patients were randomly treated with one of the two drugs. When required doses were increased and hydrochlorothiazide added until blood pressure lower than 160/95 mmHg was achieved. After this period the patients were observed for a minimum of 8 weeks. The mean length of the study was of 22 weeks. RESULTS: Both drugs significantly reduced blood pressure without modifying cardiac frequency. Doxazosin tended to favorably modify the lipid profile of the plasma while enalapril significantly reduced the levels of cholesterol, lipids and high density lipoproteins (HDL). Upon termination of the study the total HDL/cholesterol index increased 8.6% in those treated with doxazosin and decreased 5.5% in those receiving enalapril (p < 0.05). CONCLUSIONS: Although doxazosin and enalapril are potent antihypertensive drugs, the effects on plasma lipid obtained with doxazosin indicate that a reduction in cardiovascular risk was achieved with this drug in the patients included in this study.     

Amyloid beta-protein deposition in the leptomeninges and cerebral cortex

To further investigate the process of amyloid beta-protein (Abeta) deposition, we determined, using sensitive enzyme immunoassays, the levels of Abeta40 and Abeta42 (Abetas) in the soluble and insoluble fractions of the leptomeninges (containing arachnoid mater and leptomeningeal vessels) and cerebral cortices from elderly control subjects showing various stages of Abeta deposition and from patients affected by Alzheimer's disease (AD). In both locations, insoluble Abeta levels were higher by orders of magnitude than soluble Abeta levels. Soluble Abeta levels in cortices were much lower than those in leptomeninges. In insoluble Abeta in the cortex, Abeta42 was by far the predominant species, and Abeta42 in AD cortices was characterized by the highest degree of modifications in the amino terminus. In contrast, this Abeta42 predominance was not observed in insoluble Abeta in the leptomeninges, which were found to be able to accumulate Abetas to an extent similar to that in the cortex, on a weight basis. The levels of insoluble Abeta in the leptomeninges or cortex generally correlated with the degree of cerebral amyloid angiopathy or the abundance of senile plaque, respectively. However, the presence of plaque-free cortical samples showing significant levels of insoluble Abeta42 suggests that biochemically detectable Abeta accumulation precedes immunocytochemically detectable Abeta deposition in the cortex.     

Nitric oxide synthase-immunoreactive neurons in human and porcine respiratory tract

The presence of nitric oxide synthase (NO-synthase), the enzyme responsible for the production of nitric oxide (NO) from L-arginine, is shown immunocytochemically in the intrinsic neurons of the human and porcine respiratory tract. NO-synthase immunoreactivity is demonstrated in a subpopulation of neurons of the microganglia present in the wall of the extra- and intrapulmonary bronchi as well as in the hilar region of the lung in relation to blood vessels. The immunostaining was also found in some nerve fibers of the respiratory nervous system. Human and porcine lung gave similar results. The possible involvement of NO in the nonadrenergic noncholinergic (NANC) nervous regulation of the lung is discussed.