[Comparison of corneal power assessment methods after small incision lenticule extraction].

Objective: To compare the accuracy of different corneal curvature parameters in assessing the corneal refractive status and tracking corneal power changes after small incision lenticule extraction (SMILE). Methods: This prospective cross-sectional study tracked and recorded total corneal curvature parameters measured by different instruments before and three months after SMILE for myopia. These parameters, including total keratometry (TK) from the IOLMaster 700, total corneal refractive power (TCRP) from the Pentacam AXL, real keratometry (RK) from the CASIA 2, and corrected parameters calculated using the Haigis, Shammas, and Maloney methods, were compared with data obtained using the clinical history method (CHM). Surgically induced changes in TK, TCRP, and RK were analyzed and compared with those in spherical equivalent on the corneal plane (ΔSEco). Results: The study included 40 eyes (40 participants). After SMILE, the difference was smallest between TK [(0.08±0.38) D] and CHM values (P>0.05). However, TCRP, RK, KHaigis, KShammas, and KMaloney were significantly different from CHM data (P<0.05). The width of the 95% limits of agreement of TK (1.49 D) was narrowest, followed by that of RK (1.57 D). Pearson analysis showed that each parameter had a good correlation with CHM data. The differences between the changes in TK, TCRP and RK caused by surgery and ΔSEco were (0.03±0.39) D, (0.17±0.43) D, and (-0.19±0.46) D, respectively. The width of the 95% limits of agreement of ΔTK (1.54 D) was narrowest, and the correlation coefficient of ΔTK (0.951) was highest. Conclusion: The parameter TK of the IOLMaster 700 can provide accurate and objective corneal power evaluation after SMILE.

Impact of anemia on in-hospital complications after ischemic stroke.

BACKGROUND AND PURPOSE: In-hospital complications after stroke represent barriers to optimal recovery and are even potentially life-threatening. Anemia is common in stroke patients and is related to poor outcome after stroke. Less is known, however, of the association of anemia with complications. We aimed to investigate the impact of anemia on a series of in-hospital complications after ischemic stroke. METHODS: Consecutive patients with ischemic stroke within 7 days were included. Anemia on admission and its severity were defined according to World Health Organization criteria. Eight pre-specified complications, such as pneumonia, gastrointestinal bleeding (GIB) and hemorrhagic transformation, were recorded during hospitalization. RESULTS: A total of 2647 patients were included. Anemia was present in 648 patients (24.5%), and 883 patients (33.4%) experienced at least one complication. Patients with anemia were more likely to experience one or more complications, pneumonia, GIB and thromboembolism (all P < 0.001) than patients without anemia. After adjustment for the confounders, patients with anemia had an adjusted odds ratio for at least one complication of 1.539 [95% confidence interval (CI), 1.232-1.923], for pneumonia of 1.707 (95% CI, 1.345-2.167), for GIB of 2.245 (95% CI, 1.215-4.148) and for thromboembolism of 3.443 (95% CI, 1.668-7.108). The risk of at least one complication, pneumonia, GIB and thromboembolism increased with anemia severity (all P < 0.05). There was no significant association between anemia and urinary tract infection, hemorrhagic transformation, seizures and brain herniation. CONCLUSION: Anemia is an independent predictor of in-hospital complications following stroke, especially for pneumonia, GIB and thromboembolism. It remains to be studied whether prophylaxis and treatment of anemia would prevent in-hospital complications.

Childhood type 1 diabetes may increase the risk of atopic dermatitis.

BACKGROUND: Epidemiological investigations have examined the association between type 1 diabetes mellitus (T1DM) and atopic disease, but have obtained conflicting results. OBJECTIVES: To analyse the association between T1DM and atopic dermatitis (AD) in a population-based, retrospective cohort study that investigated the hypothesis that childhood T1DM is a risk factor for subsequent AD. METHODS: From claims data of the National Health Insurance programme of Taiwan, we identified 3386 patients with T1DM newly diagnosed from 1998 to 2011 and 12 725 randomly selected controls without T1DM. These were frequency matched by age, sex and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the AD risk. We used Cox proportional hazards regression models to analyse the risk of AD. RESULTS: The overall incidence rate of AD was 1·40-fold (significantly) higher in the T1DM cohort than in the non-T1DM cohort (3·31 vs. 2·35 per 1000 person years). After adjustment for potential risk factors, the overall risk of AD remained higher in the T1DM cohort [adjusted hazard ratio (HR) 1·76, 95% confidence interval (CI) 1·29-2·39] than in those without T1DM. Compared with the non-T1DM cohort, the patients with T1DM with more emergency room visits (adjusted HR 30·1, 95% CI 18·7-48·5) or hospitalizations (adjusted HR 70·3, 95% CI 45·6-114·5) had a higher risk of subsequent AD. CONCLUSIONS: This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD.

Increased Incidence of juvenile onset systemic lupus erythematosus in children with atopic dermatitis.

Herein, we investigated the risk of juvenile-onset systemic lupus erythematosus (JSLE) in children with atopic dermatitis (AD). From 2000 to 2007, 192,357 children with newly diagnosed AD and 769,428 matched non-AD controls were identified. By the end of 2008, incidences and hazard ratios (HRs) of JSLE were measured. JSLE incidence in the AD cohort was 2.90-fold greater than that in the non-AD cohort (3.25 vs. 1.12 per 100,000 person-years), with a Cox model-measured adjusted HR of 2.92 (95% CI: 1.85-4.60); the risk of JSLE was greater for older children and girls. The AD-to-non-AD cohort HR was 6.6 (95% CI: 2.88-13.1) for children aged >12 years compared with 1.81 (95% CI: 0.98-3.32) for children aged ≤ 12 years. The HR of JSLE in AD children increased from 1.55 (95% CI: 0.88-2.76) for those with ≤ 3 clinical visits to 66.3 (95% CI: 33.1-132.8) for those with >6 visits (p < 0.0001, by trend test). The risk of developing SLE in the AD cohort was the highest within five years after AD diagnosis (HR: 4.02; 95% CI: 2.83-7.08). Children with AD are at a high risk of developing JSLE during their growth period.

Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

Mortality associated with polymyalgia rheumatica in the United States in the 1999-2020 period: a multiple-cause-of-death study.

OBJECTIVE: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020. MATERIALS AND METHODS: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added. RESULTS: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend. CONCLUSIONS: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.

[Study on behavioral risk factors and lagging effect analysis with liver cancer mortality in rural critical areas of 4 provinces of China from 2009 to 2019].

Objective: To analyze the trend of liver cancer mortality in rural key areas of Jiangsu Province, Anhui Province, Shandong Province, and Henan Province (4 provinces) from 2009 to 2019 and to explore the influence of behavioral risk factors on liver cancer mortality and its lagging effect, and provide a reference for the prevention and treatment of liver cancer in China. Methods: Based on the 2009-2019 National Cause of Death Surveillance Database of the Chinese Center for Disease Control and Prevention, and the survey data of tumor and risk factor behavior of residents in key areas of 4 provinces, Joinpoint 4.2 software was used to calculate the average annual percentage change (AAPC) for assessing the temporal trend of standardized mortality of liver cancer; Chi-square test and trend Chi-square test were used to analyze the regional distribution difference and temporal change trend of behavioral habit factors. Stata 16 was used to establish a panel model to analyze the correlation and lagging effect of behavioral risk factors with liver cancer. Results: The standardized mortality rate of liver cancer in Jinhu County, Sheyang County, Lingbi County, Shou County, Mengcheng County, Wenshang County, Juye County, Luoshan County, Shenqiu County, and Xiping County showed a downward trend (AAPC<0, P<0.05) from 2009 to 2019. The consumption frequency of pickles/salted fish, red meat, and aquatic products showed a downward trend. The consumption frequency of healthy foods such as fresh vegetables, fresh fruits, and dairy products in all counties and districts showed an upward trend, and the consumption frequency of fried foods, kimchi, smoked foods, moldy foods, coffee, and soy products remained at a low level (P<0.05); but the consumption frequency of soy products and dairy products was still <20.00%. Fried food, pickles/salted fish, current smoking rate, alcohol consumption rate, and unvaccinated hepatitis B vaccine rate were positively correlated with liver cancer death, and there was a lag effect, and the lag period was 4, 1, 6, 5, 4 years respectively. Conclusions: From 2009 to 2019, the mortality rate of liver cancer in rural key areas of 4 provinces shows a downward trend. There is a correlation and lagging effect between behavioral risk factors such as fried food, smoking, and alcohol consumption and liver cancer death.

Theoretical investigation of polarization-insensitive data format conversion of RZ-OOK to RZ-BPSK in a nonlinear birefringent fiber.

Polarization-insensitive conversion of return-to-zero (RZ) ON-OFF keying (RZ-OOK) to RZ binary phase-shift keying (RZ-BPSK) has been achieved by cross-phase modulation (XPM) in a nonlinear birefringent fiber. This work presents a theoretical analysis of the dependence of format conversion on pump-probe detuning, and the pump state-of-polarization (SOP) that can fluctuate unpredictably in a realistic system. An investigation of the impact of pump polarization fluctuation on receiver sensitivity and receiver optimal threshold for the converted RZ-BPSK probe is also carried out. It was found that although the desired XPM-induced pi phase shift can be achieved by launching both the RZ-OOK pump and the probe along the same birefringent axis of the fiber, the phase shift degrades to pi/3 if the SOP of the RZ-OOK pump unpredictably switches to the other axis of the fiber, resulting in a large receiver sensitivity penalty fluctuation of 14 dB. By contrast, launching the probe at 45 degrees relative to the birefringent axes can reduce the polarization-dependent receiver sensitivity penalty fluctuation to about 2 dB as the SOP of the RZ-OOK pump is swept over the Poincaré sphere. These conclusions are in good agreement with recently.

LncRNA HOTAIR promotes colon cancer development by down-regulating miRNA-34a.

OBJECTIVE: To investigate the characteristics of long non-coding RNA (lncRNA) HOTAIR in colon cancer, and to further explore its function in the development of colon cancer and its potential regulatory mechanisms. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect HOTAIR expression in 72 colon cancer tissues along with adjacent normal tissues. Meanwhile, the relationship between HOTAIR level and colon cancer pathological parameters and patient prognosis were analyzed, respectively. QRT-PCR further verified the HOTAIR expression in colon cancer cells. Besides, knockdown and overexpression of HOTAIR models were constructed using lentivirus in HT29 and HCT-116 colon cancer cell lines. Cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EDU) and cell colony formation assays were used to analyze the effects of HOTAIR on biological function of colon cancer cell. In addition, dual luciferase reporter gene assay was performed to explore the underlying mechanisms. RESULTS: QRT-PCR results showed that HOTAIR expression in colon cancer was significantly higher than that in normal tissues. The incidence of distant metastasis was higher in patients with high expression of HOTAIR while their survival rate was lower than that of patients with low HOTAIR expression. Meanwhile, cell proliferation, invasion as well as migration ability of the cells in HOTAIR knockdown group was significantly decreased than those in the negative control group. QRT-PCR results showed that mRNA levels of miR-34a and HOTAIR in colon cancer tissues were negatively correlated. Besides, luciferase reporter gene assay revealed that overexpression of miR-34a significantly attenuated the luciferase activity of the wild-type HOTAIR vector group without attenuating the mutant HOTAIR vector group (p>0.05) In addition, the recovery experiment also found a mutual regulation between HOTAIR and miR-34a, together they could affect the malignant progression of colon cancer. CONCLUSIONS: HOTAIR expression was significantly increased in colon cancer, which was in association with distant metastasis and poor prognosis of colon cancer. In addition, HOTAIR may promote malignant progression of colon cancer by regulating miR-34a.

A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis.

We identified a novel soluble protein, mouse (m)IL-20R1a, generated by alternative splicing of the mIL-20R1 gene, which encodes one subunit of the receptor complex for mIL-19, mIL-20 and mIL-24. mIL-20R1a has 77.14% amino-acid identity with the extracellular domain of mIL-20R1. However, no significant interaction between mIL-20R1a and mIL-19 or mIL-20 was detected. Consequently, we aimed to clarify whether mIL-20R1a might function as a novel effector on certain cells. Competitive binding assays demonstrated that mIL-20R1a bound to cell surfaces and resulted in AKT and JNK phosphorylation in primary mesangial cells (MCs) isolated from either the wild-type mice, DBA/W mice, or the SLE-prone mice, NZB/W mice. NZB/W MCs expressed more mIL-20R1a transcript than DBA/W MCs did. Furthermore, mIL-20R1a-treated NZB/W MCs produced higher level of chemokines, renal fibrogenic factors and ROS than mIL-20R1a-treated DBA/W MCs did. These factors are involved in the pathogenesis of lupus nephritis. Endogenous mIL-20R1a was upregulated in the bladder, colon and spleen tissue of NZB/W mice. Elevated mIL-20R1a in the spleen tissue of NZB/W mice was expressed mainly in monocytes and B cells. mIL-20R1a further induced mIL-10 production by the anti-IgM antibody-stimulated B cells in NZB/W mice. Therefore, mIL-20R1a-mediated effects may exacerbate the disease outcome of lupus nephritis.

Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure.

Acute renal failure is an abrupt decrease in renal function. Interleukin (IL)-10 inhibits ischemic and cisplatin-induced acute renal failure. We aimed to determine whether IL-20 affects renal tubular epithelial cells and is associated with acute renal failure. We analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl(2)-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20, and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF)-beta1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1 beta transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-beta1 and IL-1 beta and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure.

Packing of transmembrane helices in bacteriorhodopsin folding: structure and thermodynamics.

We propose a coarse-grained (CG) model to study the native structure and physical properties of helical membrane proteins (HMPs) using off-lattice computer simulations. Instead of considering sequence heterogeneity explicitly, we model its effect on the packing of helices by employing a mean packing parameter r(0), which is calculated from an all-atom (AA) model. Specifically, this CG model is applied to investigate the packing of helices in bacteriorhodopsin (BR), and predicts the seven helix bundle structure of BR with a root mean square deviation (RMSD) in coordinates of helix backbone atoms (N, C, C(alpha)) of 3.99 A from its crystal structure. This predicted structure is further refined in an AA model by Amber and the refined structure has a RMSD (in coordinates of helix backbone atoms) of 2.64 A. The predicted packing position, tilting angle, and orientation angle of each helix in the refined structure are consistent with experimental data and their physical origins can be well understood in our model. Our results show that a reasonably good structure of BR can be predicted by using such a dual-scale approach, provided that its secondary structure is known. Starting from a random initial configuration, the folded structure can be obtained in days using a regular desktop computer. Various thermodynamic properties of helix packing of BR are also investigated in this CG model.

Polarization-insensitive, 40 Gb/s wavelength and RZ-OOK-to-RZ-BPSK modulation format conversion by XPM in a highly nonlinear PCF.

Polarization-insensitive wavelength conversion, as well as the conversion of return-to-zero (RZ) ON-OFF keying (RZ-OOK) to RZ binary phase-shift keying (RZ-BPSK), has been simultaneously achieved at 40 Gb/s for the first time by cross-phase modulation (XPM) in a highly birefringent, nonlinear photonic crystal fiber (PCF). A 10-9-BER receiver sensitivity conversion penalty of < 3 dB was achieved for a polarization scrambled, 40 Gb/s 25%-RZ-OOK pump, when the 40 Gb/s RZ probe was launched at 45 degrees with respect to the birefringence axes of the PCF and when the pump-probe detuning was greater than about 6 nm.

Clinical effectiveness and safety experience with alefacept in the treatment of patients with moderate-to-severe chronic plaque psoriasis in Taiwan: results of an open-label, single-arm, multicentre pilot study.

BACKGROUND: The effectiveness and safety of alefacept for the treatment of moderate-to-severe chronic plaque psoriasis has been established in several clinical trials conducted in the United States and Europe. No clinical trial of alefacept has been conducted in Asia. OBJECTIVE: To determine the effectiveness and safety of alefacept in the treatment of psoriasis in Chinese population. DESIGN AND METHODS: This was an open-label, single-arm, multicentre pilot study conducted at three centres. Patients with a body surface area > or = 10% and psoriasis area and severity Index (PASI) > or = 12 were given 15 mg alefacept intramuscularly once a week for 12 weeks and were then followed up for a further 12 weeks. RESULTS: A total of 46 patients was enrolled. Only one subject (2%) achieved a > or = 75% improvement in PASI at week 14. The median improvement in PASI at week 14 after the 12-week treatment was 39%. At any time during the 6-month course, 3 subjects (7%) achieved a Physician Global Assessment (PGA) of 'almost clear', and a > or = 50% and > or = 75% improvement in PASI was seen in 46% and 9%, respectively. There is a trend for decreased counts of CD4(+) and CD8(+) cells after alefacept treatment, but subjects who achieved PASI50 showed a lesser degree of decrease in CD4(+) and CD8(+) counts compared with those in patients who did not achieve PASI50. CONCLUSIONS: This small pilot study indicated that intramuscular alefacept was effective and safe in psoriasis in Chinese patients over 12 weeks of treatment. Further studies are needed to clarify the reason for low PASI 75 effectiveness and the paradoxical lesser decline of CD4(+) and CD8(+) T cells in those who responded.

Compartmentalization of angiotensin II generation in the dog heart. Evidence for independent mechanisms in intravascular and interstitial spaces.

Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 microM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I (1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01). ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG I (8,269+/-502 and 6, 139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.

Major depressive disorder is associated with subsequent adult-onset asthma: a population-based cohort study.

AIM: To examine the incidence of asthma in adult patients with major depressive disorder (MDD). METHODS: From the National Health Insurance database of Taiwan, we identified 30 169 adult patients who were newly diagnosed with MDD between 2000 and 2010. Individuals without depression were randomly selected four times and frequency matched for sex, age and year of diagnosis. Both cohorts were followed-up for the occurrence of asthma up to the end of 2011. Adjusted hazard ratios (aHRs) of asthma were estimated using the Cox proportional hazards method. RESULTS: The overall incidence of asthma was 1.91-fold higher in the MDD cohort than in the non-depression cohort (7.55 v. 3.96 per 1000 person-years), with an aHR of 1.66 (95% confidence interval (CI) 1.55-1.78). In both cohorts, the incidence of asthma was higher in patients and controls who were female, aged, with comorbidities and users of aspirin or beta-adrenergic receptor blockers. No significant difference was observed in the occurrence of asthma between patients with MDD treated with selective serotonin reuptake inhibitors (SSRIs) and those treated with non-SSRIs (SSRIs to non-SSRIs aHR = 1.03, 95% CI 0.91-1.17). CONCLUSION: Adult patients with MDD are at a higher risk of asthma than those without depression are.

Pharmacological studies with vinblastine in the dog.

Tritiated vinblastine was prepared by catalytic exchange and its metabolism was studied in dogs. Plasma levels of drug fell in biphasic mode with initial and secondary phase half-lives of 17 to 38 min and 3 to 5 hr, respectively. Between 28.6 and 79.1% of plasma tritium was precipitable with cold trichloroacetic acid and thus was presumably protein bound. Blood leukocytes had levels of intracellular tritium between 2.4 and 11.8 times those of the coincident plasma samples. Over a 9-day period, urinary excretion accounted for 12.1 to 16.8% and fecal excretion accounted for 30.1 to 36.1% of the administered radioactivity. Ratios of biliary to plasma radioactivity varied between 7.3 and 56.9, with unchanged vinblastine being the mamor component (46.8 to 80.7%) in the bile.

Genetic variation in angiotensin-converting enzyme does not prevent development of cardiac hypertrophy or upregulation of angiotensin II in response to aortocaval fistula.

BACKGROUND: Experimental and clinical evidence suggests that angiotensin II may be an important mediator of cardiac hypertrophy in response to hemodynamic stress. We investigated the effect of genetic variation in angiotensin-converting enzyme (ACE) on the development of cardiac hypertrophy and left ventricular (LV) dysfunction in response to volume overload. METHODS AND RESULTS: Male heterozygous ACE knockout (1/0) and wild-type (1/1) mice were studied 4 weeks after the creation of an aortocaval fistula (ACF). The LV weight/body weight ratio increased 74% in ACF versus sham-operated control mice but did not differ between genotypes. Echocardiographic circumferential stress versus rate-corrected velocity of circumferential shortening curves demonstrated depressed LV function in ACF versus sham-operated mice but no difference between genotypes. LV ACE activity was higher in 1/1 versus 1/0 mice and in ACF versus sham-operated mice, and it increased significantly more in the 1/1 versus the 1/0 mice after ACF (P<0.001 for effect of genotype, ACF/sham operation, and interaction term). LV angiotensin II was higher in ACF versus sham-operated mice but did not differ between genotypes, despite 3-fold higher LV ACE activity in ACF 1/1 versus ACF 1/0 mice. CONCLUSIONS: ACE underexpression does not prevent cardiac hypertrophy or LV dysfunction in response to volume overload. LV angiotensin II is unaffected by ACE genotype, both at baseline and after volume overload, indicating that the heart can maintain angiotensin II levels across a broad range of genetic ACE variation under both physiological and pathophysiological conditions.