Demonstration of a trapped-ion atomic clock in space.

Atomic clocks, which lock the frequency of an oscillator to the extremely stable quantized energy levels of atoms, are essential for navigation applications such as deep space exploration1 and global navigation satellite systems2, and are useful tools with which to address questions in fundamental physics3-6. Such satellite systems use precise measurement of signal propagation times determined by atomic clocks, together with propagation speed, to calculate position. Although space atomic clocks with low instability are an enabling technology for global navigation, they have not yet been applied to deep space navigation and have seen only limited application to space-based fundamental physics, owing to performance constraints imposed by the rigours of space operation7. Methods of electromagnetically trapping and cooling ions have revolutionized atomic clock performance8-13. Terrestrial trapped-ion clocks operating in the optical domain have achieved orders-of-magnitude improvements in performance over their predecessors and have become a key component in national metrology laboratory research programmes13, but transporting this new technology into space has remained challenging. Here we show the results from a trapped-ion atomic clock operating in space. On the ground, NASA's Deep Space Atomic Clock demonstrated a short-term fractional frequency stability of 1.5 × 10-13/τ1/2 (where τ is the averaging time)14. Launched in 2019, the clock has operated for more than 12 months in space and demonstrated there a long-term stability of 3 × 10-15 at 23 days (no drift removal), and an estimated drift of 3.0(0.7) × 10-16 per day. Each of these exceeds current space clock performance by up to an order of magnitude15-17. The Deep Space Atomic Clock is particularly amenable to the space environment because of its low sensitivity to variations in radiation, temperature and magnetic fields. This level of space clock performance will enable one-way navigation in which signal delay times are measured in situ, making near-real-time navigation of deep space probes possible18.

[A physician-patient survey for primary immune thrombocytopenia: Chinese subgroup analysis of I-WISh International Survey].

Objective: To explore the impact of primary immune thrombocytopenia (ITP) on patient's quality of life and emotional well-being, and both the physician and the patient's perception of the treatment. Methods: This study was a Chinese Subgroup analysis of I-WISh survey, including 102 physicians and 286 ITP patients invited to complete the survey. A descriptive analysis of the results of the physician-patient survey was conducted in three parts: symptoms, impact of ITP on quality of life and emotion, and treatment perception. Results: Fatigue and anxiety about unstable platelet counts were the main symptoms after treatment. Physicians reported inadequate frequency of anxiety and fatigue. In terms of quality of life, over 90.0% of patients thought that ITP had a negative impact on their working life/studies, daily tasks, energy, capacity to exercise, and sexual life. With regard to emotion, 60.8% (174/286) patients thought that ITP had a greater impact on overall emotion, concerns about the fluctuation in platelet level (74.8%, 214/286) , disease itself (71.7%, 205/286) and disease progression (68.9%, 197/286) were the common issues, which were similar to the physicians' evaluations. Both physicians and patients agreed that reducing spontaneous bleeding, maintaining a healthy blood count and improving quality of life were the top three important treatment goals. Physicians considered reducing bleeding risk as the most important factor for decision making. Physicians believed that patients receiving glucocorticoid (54.9%, 56/102) were most likely to succeed in achieving sustained response while patients had the best response to thrombopoietin receptor agonist (TPO-RA) treatment, with about 83.9% (240/286) being satisfied with the overall effectiveness of TPO-RA. Conclusions: Physicians in the I-WISh Chinese subgroup had low awareness on patients' fatigue and anxiety. The quality of life and emotion of patients were significantly negatively affected by ITP. There are differences in the selection of treatments between physicians and patients, suggesting that physicians should raise concerns about the quality of life of ITP patients and make individualized treatment options through physician-patient shared decisions.

Preoperative mean platelet volume and platelet distribution associated with thyroid cancer.

Thyroid cancer is the most frequent cancer of the endocrine glands and the fifth most frequent cancer in women. Activated platelets play a crucial role in thrombosis, inflammation, and cancer. Mean platelet volume (MPV) and platelet distribution width (PDW) are early index of platelet activation. The purpose of this study is to investigate platelet indices levels in thyroid cancer. The study enrolled 280 patients with thyroid cancer and 280 control subjects. Patients' characteristics and hematologic tests data were collected at the time of diagnosis. Correlations between platelet indices and clinical characteristics were analyzed. The odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid cancer were calculated using multivariate logistic regression analyses across MPV and PDW quartiles. The patients with thyroid cancer had lower MPV and higher PDW compared with control subjects. MPV was correlated with tumor-nodus-metastases (TNM) stage and lymph node metastasis. Moreover, after adjusting for other risk factors, the prevalence risk of thyroid cancer for the lowest quartile of MPV was 7.242 (4.069-12.887) (P < 0.001) and for the highest quartile of PDW was 6.065 (3.321-11.076) (P < 0.001), respectively. The study showed that the patients with thyroid cancer have lower MPV and higher PDW compared to control subjects. Moreover, MPV and PDW were independently associated with the presence of thyroid cancer. Further studies are needed to evaluate the utility of MPV and PDW as novel diagnostic screening tools for thyroid cancer.

Determination of phloroglucinol by HPLC-MS/MS and its application to a bioequivalence study in healthy volunteers.

OBJECTIVE: The aim of this study was to compare the pharmacokinetic characteristics of phloroglucinol between an orally disintegrating tablet and an orally lyophilized tablet of phloroglucinol in healthy volunteers under fasting condition. PATIENTS AND METHODS: A rapid and simple method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the determination of phloroglucinol in human plasma. The plasma sample was prepared by liquid-liquid extraction, and paracetamol was chosen as the internal standard. Phloroglucinol and IS were separated on a C18 column with a mobile phase consisted of methanol/water (80:20 v/v) with 0.02% formic acid. HPLC-MS/MS analyses were performed on a triple- quadruple tandem mass spectrometer by monitoring protonated parent→daughter ion pairs at m/z 125.0→56.9 for phloroglucinol, and m/z 150.2→107.0 for paracetamol (IS). The method was the high sensitivity with a lower limit of quantification (LLOQ) of 1.976 ng/mL. RESULTS: Drug and IS were detected by HPLC/MS/MS with negative electrospray ionization (ESI). Accuracy and precision for the assay were determined by calculating the intra- and inter-batch variation of quality control (QC) samples at three concentration levels. The relative standard deviation (RSD) was less than 15.0%. The detection and quantitation of drug and IS within 4.5 min make this method suitable for high-throughput analyses. In this study, the Cmax of phloroglucinol were calculated to 515.6 ± 134.4 ng/mL and 536.0 ± 144.8 ng/mL for the test drug and the reference drug, respectively. The AUC0-t values were 459.5 ± 81.03 ng·mL-1·h and 491.8 ± 95.17 ng·mL-1·h for the test drug and the reference drug; 24 subjects completed the study, respectively. The geometric mean ratio (GMR) and the 90% confidence intervals (CIs) of Cmax and AUC0-t of phloroglucinol were 97.1 (90.2-103.9) and 93.8 (88.7-99.2), respectively. CONCLUSIONS: The method was employed for the first time during pharmacokinetic studies of phloroglucinol in human plasma following a single dose of phloroglucinol 160 mg tablets. There was no significant difference in pharmacokinetic profiles between the two treatments.

[Diagnostic value of carotid atherosclerosis score for ischemic stroke].

OBJECTIVE: To discuss the diagnostic value of carotid atherosclerosis score for ischemic stroke. METHODS: In the study, 151 patients with ischemic stroke were enrolled, who were diagnosed by cranial CT scan or cranial MRI scan, and examined with carotid duplex ultrasound, and 151 healthy check-up cases matched by age and sex were chosen as control group, who were excluded ischemic stroke by cranial CT scan or cranial MRI scan. All the control cases were examined with carotid duplex ultrasound also. Intima-media thickness (IMT), the number of carotid plaques, the size of each plaque, the location of the plaque and each plaque's echo, texture, surface regularity were estimated by carotid duplex ultrasound. RESULTS: The IMT of the case group and the control group were (0.946±0.185) mm and (0.863±0.148) mm, and there were significant differences (P<0.001); The parameters of arterial plaque correlated with ischemic stroke were plaque's echo, texture and surface regularity, however the plaque size and location were not correlated with ischemic stroke. The median and quartile of carotid artery plaque score were 3 and 2 respectively in case group, 1 and 2 respectively in control group, and there were significant differences (P<0.001); The parameters of carotid arterial atherosclerosis associated with ischemic stroke were carotid artery plaque score,carotid stenosis degree and IMT, but not the number of carotid plaques. The median and quartile of carotid arterial atherosclerosis score were 5 and 4 respectively in case group, 2 and 4 respectively in control group, and there were significant differences (P<0.001); The area under the curve (AUC) for IMT, the number of carotid plaques, carotid artery plaque score and carotid arterial atherosclerosis score were 0.679, 0.677, 0.704 and 0.805,respectively (P<0.001). The accuracy of carotid atherosclerosis score was the highest. CONCLUSION: Carotid artery plaque score and carotid atherosclerosis score can be used for the diagnosis of ischemic stroke, and the accuracy of carotid atherosclerosis score is higher.

Bone mineral density is associated with left ventricular diastolic function in men with type 2 diabetes.

AIMS: Type 2 diabetes (T2DM) is associated with chronic heart failure and cardiomyopathy. Furthermore, low bone mineral density (BMD) predicts incident heart failure. Abnormal diastolic function reflects early changes in cardiac function and plays a key role in the development of heart failure. The purpose of this study was to investigate the association between BMD with left ventricular (LV) diastolic function in men with T2DM. METHODS: In all, 344 men with T2DM and 331 age-matched control subjects were enrolled. BMD measurements were performed. LV diastolic function and structure were assessed by echocardiographic evaluation. RESULTS: BMD was lower in men with T2DM than in controls. There were significant differences in the level of parameters reflecting cardiac structure and LV diastolic function between two groups. Moreover, LV diastolic function and structure parameters also showed significant differences as BMD reduced in T2DM group. BMD at femoral neck was correlated with LV diastolic function parameters in T2DM after adjusting for confounding factors. Multivariable logistic analysis revealed that osteopenia and osteoporosis were associated with diastolic dysfunction compared to the control in men with T2DM. However, no association between BMD and LV diastolic function was found in subjects without T2DM. CONCLUSION: Osteoporosis may be an independent factor for LV diastolic dysfunction in men with T2DM. Our data suggested that early detection of abnormal BMD should warrant for early search of undetected LV diastolic dysfunction in diabetic men.

Non-alcoholic fatty liver disease is associated with progression of arterial stiffness.

BACKGROUND AND AIMS: NAFLD is an independent risk factor for increased cardiovascular disease. Arterial stiffness is an index of subclinical atherosclerosis. The aims of this study were to examine prospectively the relationship between Non-alcoholic fatty liver disease (NAFLD) and the progression of arterial stiffness. METHODS AND RESULTS: A prospective study of 728 men and 497 women free of hypertension, and diabetes at the baseline were conducted. The subjects were followed for 5 years. The progression rate of arterial stiffness was measured by calculating the increase in brachial-ankle pulse wave velocity (baPWV) the changes of the baPWV (adjusted for age) during the study period was significantly greater in the patients with NAFLD (172.4 ± 42.1 cm/s for men, 95.8 ± 36.7 cm/s for women) than in the subjects without NAFLD (70.3 ± 56.5 cm/s for men, 55.4 ± 42.2 cm/s for women). For the subjects with metabolic syndrome, after adjusting for multiple risk factors, NAFLD was a significant predictor of baPWV progression (for male, ß = 0.843; P < 0.001; for female, ß = 0.575; P < 0.001, respectively). In addition, results were unmodified in subjects without metabolic syndrome. CONCLUSIONS: NAFLD was found to be an independent predictor of faster progression of baPWV even after adjusting other cardiovascular risk factors. These prospective data support a pathogenic role for NAFLD in the development of arterial stiffness.

Elevated mean platelet volume is associated with silent cerebral infarction.

BACKGROUND: The presence of silent cerebral infarction (SCI) increases the risk of transient ischaemia attack, symptomatic stroke, cardiovascular disease and dementia. Mean platelet volume (MPV) is a surrogate marker of activated platelets and is considered a link between inflammation and thrombosis. In addition, MPV is a risk predictor for cardiovascular disease, stroke and overall vascular mortality. AIMS: The purpose of the study was to assess the MPV levels in SCI patients. METHODS: A cross-sectional study was conducted to evaluate the association between MPV and SCI in 2215 subjects (1385 men and 830 women). RESULTS: The participants with SCI had higher MPV levels than those without SCI (10.4 ± 1.3 fL vs. 9.2 ± 1.2 fL; P < 0.001). Moreover, the subjects with a high MPV had a higher prevalence of SCI. Multivariate logistic regression analyses revealed that the odds ratios and 95% confidence intervals for SCI according to MPV quartiles were 1.000, 2.131 (1.319-3.444), 3.015 (1.896-4.794), 7.822 (4.874-12.554) respectively (P < 0.001). CONCLUSION: MPV is a novel index for SCI regardless of classical cardiovascular risk factors.

Decreased serum bilirubin is associated with arterial stiffness in men.

BACKGROUND AND AIMS: The brachial-ankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. Serum total bilirubin (TB) is an effective antioxidant and has been associated with carotid intima-media thickness, cardiovascular disease, stroke and peripheral arterial disease, all of which may be caused by arteriosclerosis. This study aimed to investigate the association of TB with arterial stiffness. METHODS AND RESULTS: In this cross-sectional study, we investigated the relationship between TB and baPWV in 2207 participants (1331 men, 876 women) in a general health examination. Different metabolic parameters were compared across TB quartiles. Age-adjusted mean values of baPWV gradually decreased with TB quartiles in men (Q1 = 1348, Q2 = 1266, Q3 = 1215, and Q4 = 1154 cm/s). However, the age-adjusted means of baPWV had no significance in women according to TB quartiles. Univariate analysis showed that age, smoking status, BMI, SBP, DBP, AST, ALT, GGT, TB, TG, and HDL-C were significantly associated with baPWV in men, whereas only age, BMI, SBP, DBP, TG and FPG were significantly associated with baPWV in women. In addition, BMI, SBP, TB, age, TG, and AST were significant factors in the multivariate model with baPWV in men; only BMI and FPG were significant factors with baPWV in women. CONCLUSION: The findings show that serum total bilirubin concentration is negatively correlated to arterial stiffness in Chinese men. Early detection of abnormal bilirubin levels could potentially serve as an early biomarker for arterial stiffness.

Atrophy and intestinal metaplasia one year after cure of H. pylori infection: a prospective, randomized study.

BACKGROUND & AIMS: Helicobacter pylori-infected gastric mucosa evolves through stages of chronic gastritis, intestinal metaplasia (IM), glandular atrophy (GA), and dysplasia before carcinoma develops. We studied if H. pylori eradication would alter the course of premalignant histologic changes in the stomach. METHODS: Volunteers from the Yantai County in China underwent upper endoscopy with biopsy specimens obtained from the antrum and corpus. H. pylori-infected subjects were randomized to receive either a 1-week course of omeprazole, amoxicillin, and clarithromycin (OAC) or placebo. At 1 year, endoscopies with biopsies were repeated. RESULTS: A total of 587 H. pylori-infected subjects were randomized to OAC (n = 295) and placebo (n = 292). At 1 year, H. pylori was eradicated in 226 subjects assigned to OAC. In the placebo group, 245 patients remained H. pylori infected. Analysis of paired samples obtained from the same patients showed that acute and chronic gastritis decreased in both the antrum and corpus after H. pylori eradication (P<0.001) and activity of IM decreased in antrum (P = 0.014). In the H. pylori-infected group, antral biopsy specimens had more pronounced acute gastritis (P = 0.01), whereas corpus specimens showed increased acute and chronic gastritis (P<0.001) and a marginal increase in GA (P = 0.052). When histologic changes were compared between the 2 groups, decrease in acute and chronic gastritis was more frequent after H. pylori eradication (P<0.001) but changes in IM were similar. In the H. pylori-infected group, increase in GA was seen in the corpus (P = 0.01). CONCLUSIONS: At 1 year, H. pylori eradication is beneficial in preventing progression of pathologic changes of the gastric mucosa.

Identification of resilin in the leg of cockroach, Periplaneta americana: confirmation by a simple method using pH dependence of UV fluorescence.

We have examined the tarsus (foot) and tibial segments of the cockroach leg to identify structures that contain the elastic protein resilin. The presence of resilin was tested using the conventional criteria of fluorescent emission at 420 nm under UV illumination and histological staining of wholemount tissues by toluidine blue. We have also developed a simple method of confirming identification of resilin through changes in its fluorescence that occur with alteration of pH of the surrounding medium. Using a commonly available excitation filter that only passes light at >330 nm, we found that the emission was present at neutral pH but was eliminated at low pH. It then reversibly reappeared when medium of higher pH was restored. This effect is attributable to a known shift in the absorption maximum of amino acids of resilin that occurs in acidic media (from 330 to 285 nm). The accuracy of this method of identification was confirmed by examination of ligaments of the wing hinge, which has previously been shown to contain resilin in a number of insects. Using these techniques, we have identified resilin in association with ligaments at the tibio-tarsal joint and in the articulation between the fourth and fifth tarsal segments of the leg. The anatomical arrangement of these ligaments suggests that they could aid in the generation of leg movements during walking by functioning as elastic antagonists to the actions of leg muscles. The method of identification we have devised could readily be applied to aid in the localization of resilin in other animals.

Application of YLD calculation in assessing disease data--an analysis of 4 diseases in 2 regions.

The objective of the current study is to discuss the problems related to how data is used to calculate Years Lost with Disability (YLD) with the method recommended by the World Bank. The study includes collecting useful data, estimating disease duration and average age of disease onset, adjusting incidence and prevalence data by means of a software programme, DISMOD (Harvard University Incidence & Prevalence Model), and assessing the importance of YLD calculation for different diseases. Remission and fatality rates of 3 diseases were estimated by experts at 2 round consultations. Incidence rates, disease duration and average age of disease onset were calculated and adjusted by DISMOD. YLD due to schizophrenia is the highest among 4 diseases in two regions. YLD is 18.88% in disability adjusted life year for 4 diseases in Xiacheng District, and 19.97% in Fuyang County. Available data can be used for the calculation of YLD after being adjusted. DISMOD is a useful instrument to test the internal consistency of incidence, prevalence, remission and fatality rate. The adjusted data are acceptable to experts and DISMOD. To get rational remission and fatality rates, we can use a cohort method through expert consultations. To reflect overall burden of disease, YLD calculation should be used.

Gender differences in acute N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA) nephrotoxicity in Fischer 344 rats.

N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide that induces nephrotoxicity as its major toxicity. NDPS is also a more potent nephrotoxicant in female than in male rats. The purpose of this study was to examine the nephrotoxic potential of the two NDPS metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA) in age-matched male and female Fischer 344 rats to determine if gender differences exist for the nephrotoxicity induced by the two NDPS metabolites. Rats (4 per group) were administered a single intraperitoneal (ip) injection of NDHS or 2-NDHSA (0.025 or 0.05 mmol/kg) or vehicle, and renal function was monitored for 48 h. Neither compound induced significant nephrotoxicity in male rats at the doses tested. However, in female rats both metabolites induced marked nephrotoxicity at the 0.05 mmol/kg dose level, and treatment with 0.025 mmol/kg 2-NDHSA induced some changes in renal function (transient diuresis, transient proteinuria, decreased organic ion accumulation). Little effect on renal function was induced in females by treatment with 0.025 mmol/kg NDHS. At toxic levels in female rats, the renal lesions were located primarily in the S2 and S3 segments of the proximal tubule. These results indicate that, like the parent compound, gender differences exist in the nephrotoxic potential of NDHS and 2-NDHSA. The results also suggest that in females, as in males, NDPS nephrotoxicity is mediated via NDHS and/or 2-NDHSA. However, it is not clear if the ultimate nephrotoxicant species following NDPS exposure is different in males and females or if the same ultimate nephrotoxicant species is produced in both species but handled differently by male and female kidneys. Thus, further studies are needed to determine the exact nature of the ultimate nephrotoxicant species and the mechanisms of the observed gender differences.

Case-control study of diet and prostate cancer in China.

INTRODUCTION: A higher incidence of prostate cancer is observed in the Western world than in Asian countries. Although it is relatively rare in China, an increased incidence has been reported in recent years. Studies in high-risk populations have suggested that dietary fat may play a role in enhancing the risk of developing prostate cancer. However, limited epidemiologic study has never examined the role of diet in low risk populations. METHODS: A case-control study was conducted in 12 cities in China to evaluate the relationship between dietary factors and prostate cancer risk. We conducted personal interviews with 133 histopathologically confirmed prostate cancer cases diagnosed between 1989 to 1992 and 265 neighborhood controls of similar age. RESULTS: Cases were more likely than controls to consume food with high fat and from animal sources (p < 0.01). The daily fat intake and the percentage of energy from fat were statistically significantly higher among cases than among controls (p < 0.01). The adjusted odds ratio for total fat between lowest quartiles and highest quartiles was OR = 3.6 (95 percent C.I. 1.8-7.2); for saturated fat, OR = 2.9 (95 percent C.I. 1.5-5.7); and for unsaturated fat, OR = 3.3 (95 percent C.I. 1.7-6.3). DISCUSSION: The data suggest that dietary fat, both saturated and unsaturated, are associated with an increased risk for prostate cancer in a low risk population.

Application of the exact solution for scattering by an infinite cylinder to the estimation of scattering by a finite cylinder.

A new algorithm for cylindrical Bessel functions that is similar to the one for spherical Bessel functions allows us to compute scattering functions for infinitely long cylinders covering sizes ka = 2πa/λ up to 8000 through the use of only an eight-digit single-precision machine computation. The scattering function and complex extinction coefficient of a finite cylinder that is seen near perpendicular incidence are derived from those of an infinitely long cylinder by the use of Huygens's principle. The result, which contains no arbitrary normalization factor, agrees quite well with analog microwave measurements of both extinction and scattering for such cylinders, even for an aspect ratio p = l/(2a) as low as 2. Rainbows produced by cylinders are similar to those for spherical drops but are brighter and have a lower contrast.

Vasectomy and prostate cancer risk in China.

Vasectomy has been reported to be associated with an increased risk of prostate cancer in western countries. A hospital-based case-control study was conducted in 12 cities in China to evaluate the relationship between vasectomy and prostate cancer risk in China, a low-risk country with rising incidence and increasing use of vasectomy. Interviews were conducted with 138 histologically confirmed prostate cancer cases diagnosed during 1989-1992 and 638 controls (158 hospital cancer, 158 hospital noncancer, and 322 neighborhood controls) of similar ages. Vasectomy at least 10 years prior to interview was reported by 10% of the cases versus 3% of the controls. Odds ratios for prostate cancer associated with vasectomy were 2.0 (95% confidence interval, 0.7-6.1), 3.3 (95% confidence interval, 1.0-11.3), and 6.7 (95% confidence interval, 2.1-21.6), respectively, when hospital cancer, hospital noncancer, and neighborhood controls were used for comparison. Although detection bias is of concern, the data suggest that in China, men with a history of vasectomy may experience an increased risk of prostate cancer.

PIP: This paper reports the findings of a hospital-based case-control study that was conducted at major teaching hospitals in 12 cities in China. China reports the lowest incidence in prostate cancer of over 100 registries reporting cancer incidence. This investigation evaluated the relationship between vasectomy and prostate cancer and attempted to identify any etiological factor. A total of 138 study patients (index cases) were identified. Controls used in this study included a cancer control and a noncancer control from the same hospital, and 2 neighborhood controls. Chances of having prostate cancer were statistically determined by logistic regression analysis with age group adjustments made. The analysis reviewed 138 cases and 638 controls. Results indicate that, regardless of the variable control used for comparison, an increased risk of prostate cancer was associated with having had a vasectomy. Statistical odds ratio was 2.0 for hospital cancer controls (95% confidence interval [CI]; 0.7-6.1); 3.3 for hospital noncancer controls (95% CI; 1.0-11.3); and 6.7 for neighborhood controls (95% CI; 2.1-21.6). The authors conclude that, as reported for men in Western countries, Chinese men who have had a vasectomy are at significantly increased risk for developing prostate cancer compared to men who never have had a vasectomy. They report a near 2-fold increase in risk (vasectomy vs. non-vasectomy) in developing the disease. Conclusions about cause and effect are premature, but these findings warrant further investigation of several issues. These include: changes in the endocrine system due to vasectomy; systematic and local immunity changes after vasectomy; and other possible biochemical factors that enhance/inhibit cancer growth in the prostate gland.

In vivo and in vitro 4-amino-2,6-dichlorophenol nephrotoxicity and hepatotoxicity in the Fischer 344 rat.

Halogenated anilines and aminophenols are nephrotoxicants and hepatotoxicants in mammals. The purpose of this study was to determine the in vivo and in vitro nephrotoxic and hepatotoxic potential of 4-amino-2,6-dichlorophenol, a putative metabolite of 3,5-dichloroaniline. In the in vivo experiments, male Fischer 344 rats (four/group) were administered a single intraperitoneal (i.p.) injection of 4-amino-2,6-dichlorophenol (0.25, 0.38 or 0.50 mmol/kg) or vehicle (dimethylsulfoxide (DMSO), 1.0 ml/kg) and renal and hepatic function monitored for 48 h. Only minor changes in function or morphology were observed in the 0.25 mmol/kg treatment group. However, in the 0.38 mmol/kg treatment group evidence of both nephrotoxicity and hepatotoxicity were evident. Nephrotoxicity was characterized by increased proteinuria, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased p-aminohippurate (PAH) accumulation and proximal tubular necrosis in the corticomedullary region of the kidney. Hepatotoxicity was characterized by elevated plasma alanine aminotransferase (ALT/GPT) activity and liver weight. Animals administered the 0.5 mmol/kg dose died within 24 h. In the in vitro experiments, the effect of 4-amino-2,6-dichlorophenol on organic ion accumulation, gluconeogenesis and lactate dehydrogenase (LDH) leakage was quantitated in liver and/or renal cortical slices. Organic anion accumulation was inhibited in renal cortical slices by 4-amino-2,6-dichlorophenol bath concentrations of 5 x 10(-6) M or higher, while organic cation uptake was decreased at 4-amino-2,6-dichlorophenol bath concentrations of 1 x 10(-5) M or greater. Renal and hepatic pyruvate-stimulated gluconeogenesis were inhibited and renal LDH leakage increased at 4-amino-2,6-dichlorophenol bath concentrations of 5 x 10(-5) M or greater. Increased LDH leakage from liver slices was not observed. These results demonstrate that 4-amino-2,6-dichlorophenol is a nephrotoxicant and hepatotoxicant in vivo and in vitro and that the kidney is more susceptible to 4-amino-2,6-dichlorophenol toxicity than the liver.

Studies on the concentrations of arsenic, selenium, copper, zinc and iron in the hair of blackfoot disease patients in different clinical stages.

Flame atomic absorption spectrophotometric methods were developed for, arsenic, selenium, copper, zinc and iron in hair samples. Data from blackfoot disease patients at five clinical stages were compared with those from healthy controls. The copper and zinc concentrations showed only slight differences in all clinical stages, which indicated the less relation to blackfoot disease. The decrease of selenium and iron in all stages was attributed to the antagonistic effect of arsenic; arsenic increased in the first and second stages, but decreased in the later stages. The decrease of selenium and iron during the progression of the disease is thought to be due to persistence of the antagonistic effect of arsenic in the initial stages, so that very low concentrations of selenium are found in the advanced stages, despite the later decrease of arsenic. There was also a progressive decrease of iron with advance of the disease, and the later stages also showed a decrease in haemoglobin. It was shown that arsenic is a major cause of blackfoot disease, and that it antagonises selenium and iron, which decreased in the advanced clinical stages of the disease.