Synthesis and excretion profile of 1,4- [14C]phenylenebis(methylene)selenocyanate in the rat

1,4-Phenylenebis(methylene)selenocyanate (p-XSC) inhibits chemically induced tumors in several laboratory animal models. To understand its mode of action, we synthesized p-[14C]XSC, examined its excretion pattern in female CD rats and also the nature of its metabolites. p- [14C]XSC was synthesized from alpha,alpha-dibromo-p-[ring-14C]xylene in 80% yield. The excretion profile of p-[14C]XSC (15.8 mg/kg body wt, 200 microCi/rat, oral administration, in 1 ml corn oil) in vivo was monitored by measuring radioactivity and selenium content. On the basis of radioactivity, approximately 20% of the dose was excreted in the urine and 68% in the feces over 3 days. The cumulative percentages of the dose excreted over 7 days were 24% in urine and 75% in feces, similar to excretion rates of selenium. According to selenium measurement, <1% of the dose was detected in exhaled air; radioactivity was not detected. Only 15% of the dose was extractable from the feces with EtOAc and was identified as tetraselenocyclophane (TSC). Most of the radioactivity remained tightly bound to the feces. Approximately 10% of this bound material converted to TSC on reduction with NaBH4. Organic soluble metabolites in urine did not exceed 2% of the dose; sulfate (9 % of urinary metabolites) and glucuronic acid (19.5% of urinary metabolites) conjugates were observed but their structural identification is still underway. Co-chromatography with a synthetic standard led to the detection of terephthalic acid (1,4- benzenedicarboxylic acid) as a minor metabolite. The major urinary conjugates contained selenium. Despite the low levels of selenium in the exhaled air, the reductive metabolism of p-XSC to H2Se cannot be ruled out. Identification of TSC in vivo indicates that a selenol may be a key intermediate responsible for the chemopreventive action of p- XSC.      

Enteroviruses as a possible cause of hypertension,dilated cardiomyopathy (DCM) and hypertensive heart failure (HHF) in South western Nigeria

Background

Human enteroviruses have long been associated with various diseases of man resulting into a wide range of acute symptoms involving the cardiac and skeletal muscles, central nervous system, pancreas, skin and mucous membranes.

Objective

To assess the role of enteroviruses in the etiology of hypertension, DCM and HHF.

Methods

We obtained stool specimens from 70 subjects comprising 65 patients and 5 controls and isolation was carried out on RD, L20B, HEp-2C and Vero cell lines and identified by neutralization with standard antisera (RIVM). Thirty-six enteroviruses were isolated and identified to be Coxsackieviruses-B5, A9, Echoviruses 1, 6, 7, 9, 11, 12, 22, 30 and Poliovirus type 1 and 3.

Results

Three most frequently occurring enterovirus serotypes which constitute 60.0% of the 30 NPEV typed and 50.0% of all the isolates were Echoviruses, Coxsackie-B5-virus and Coxsackievirus-A9. Echoviruses constituted 50.0% of all the serotypes while Coxsackieviruses-B5 and A9 accounts for the 27.8 % and 5.6% respectively. Enteroviral isolation rate was higher in age groups 51 years and above. The percentage of study subjects who had Coxsackie-B5-viruses and echoviruses was significantly (P<0.05) higher in cases of hypertension, HHF and DCM than in control subjects. Coxackie-B5-virus, Echovirus-6 and Echovirus-11 were found in both study locations.

Conclusion

The findings of this study showed that Enteroviruses may likely be involved in the etiology of hypertension, DCM and HHF. Further studies would therefore be necessary for the prevention and control of these diseases.     

Antimicrobial potential of Actinomycetes species isolated from marine environment

Objective

To evaluate the antimicrobial activity of Actinomycetes species isolated from marine environment.

Methods

Twenty one strains of Actinomycetes were isolated from samples of Royapuram, Muttukadu, Mahabalipuram sea shores and Adyar estuary. Preliminary screening was done using cross-streak method against two gram-positive and eight gram-negative bacteria. The most potent strains C11 and C12 were selected from which antibacterial substances were extracted. The antibacterial activities of the extracts were performed using Kirby-Bauer disc diffusion method. Molecular identification of those isolates was done.

Results

All those twenty one isolates were active against at least one of the test organisms. Morphological characters were recorded. C11 showed activity against Staphylococcus species (13.0±0.5 mm), Vibrio harveyi (11.0±0.2 mm), Pseudomonas species (12.0±0.3 mm). C12 showed activity against Staphylococcus species (16.0±0.4 mm), Bacillus subtilis (11.0±0.2 mm), Vibrio harveyi (9.0±0.1 mm), Pseudomonas species (10.0±0.2 mm). 16S rRNA pattern strongly suggested that C11 and C12 strains were Streptomyces species.

Conclusions

The results of the present investigation reveal that the marine Actinomycetes from coastal environment are the potent source of novel antibiotics. Isolation, characterization and study of Actinomycetes can be useful in discovery of novel species of Actinomycetes.     

Blood pressure in children and target-organ damage later in life

The aim of this study was to examine the association between blood pressure (BP) in children and adolescents and cardiovascular and renal disease in adulthood. This was a retrospective study on patients <18 years of age with an elective admission to Landspitali University Hospital in Reykjavik, Iceland, between 1950 and 1967. We recorded baseline variables including BP and invited all patients for a follow-up visit in 2008 for repeat studies. We used χ², Fisher’s exact test, and logistic regression to examine the association between BP in childhood and outcome variables at follow-up. We identified 126 individuals (54 men) for the study. The median age (range) at childhood admission was 15 (10–17) years and the median BP was 125/80 mmHg. Median age at follow-up was 58 (42–68) years, follow-up time 43 (25–52) years, and median BP 133/75 mmHg. Eleven had died (five men) and 49 had been diagnosed with hypertension (23 men) and 12 with coronary artery disease (ten men). There was a significant correlation between the diagnosis of coronary artery disease at follow-up and childhood systolic BP (odds ratio?=?1.052; P?=?0.03) as well as systolic BP?≥?95th percentile (P?=?0.03). Our results suggest that elevated childhood systolic BP may increase the risk of coronary artery disease in adult life. The sample size is a limiting factor, and the study should be carried out in a larger population.     

Acute kidney injury with renal replacement therapy in trauma patients

Background: Acute kidney injury (AKI) with renal replacement therapy (RRT) is rare in trauma patients. The primary aim of the study was to assess incidence, mortality and chronic RRT dependency in this patient group. Methods: Adult trauma patients with AKI receiving RRT at a regional trauma referral center over a 12‐year period were retrospectively reviewed. Results: Population‐based incidence of post‐traumatic AKI with RRT was 1.8 persons per million inhabitants per year (p.p.m./year) [95% confidence the interval (CI) 1.5–2.1 p.p.m./year]. In trauma patients admitted to hospital, incidence was 0.5‰ (95% CI 0.3–0.7‰) of those treated in intensive care unit (ICU), it was 8.3% (95% CI 5.9–10.8%). The median age was 46 years. Odds ratio (OR) for post‐traumatic AKI requiring RRT was higher in males than in females in general population (OR 5.6, 95% CI 2.2–14.0), and in trauma patients admitted to hospital (OR 4.4, 95% CI 1.9–10.3) and ICU (OR 4.5, 95% CI 1.9–10.7). The in‐hospital mortality rate was 24% (95% CI 11–37%), 3‐month mortality 36% (95% CI 21–51%) and 1‐year mortality 40% (95% CI 25–55%). Age was a risk factor for death after 1 year, with 57% (95% CI 7–109%) increased risk for each 10 years added. None of the survivors was dialysis‐dependent 3 months or 1 year after trauma. Conclusion: AKI in trauma patients requiring RRT was rare in this single‐center study. More males than females were affected. Mortality was modest, and renal recovery was excellent as none of the survivors became dependent on chronic RRT.     

The crown-rump length in early human pregnancy: a reappraisal

Summary. The crown-rump length (CRL) was measured by means of transvaginal sonography in 41 pregnancies resulting from in-vitro fertilization (IVF). The embryonic CRL could be determined as early as 25 days after follicle aspiration. A reference chart was constructed relating the CRL to the number of days following follicle aspiration. Comparison with the CRL chart by Robinson & Fleming (1975) currently in use revealed that transvaginal sonography allows earlier and more accurate measurement of embryonic CRL.     

The Effect of Sodium Depletion and Potassium Supplementation on Vasopressin,Renin and Catecholamines in Hypertensive Men

ABSTRACT Seventeen 50-year-old hypertensive men (157±4/110±2 mmHg, mean ± SE) were given low sodium diet for one week, which was supplemented with potassium the following week. The urinary Na⁺/K⁺ excretion ratio changed from 2:1 to 1:5 and 1:12, respectively, during dietary intervention. Arterial plasma vasopressin decreased by 3.4±1.7 ng/l (0.05>p<0.10) and urinary excretion of vasopressin was reduced by nearly 50% (p<0.001) during sodium depletion, while plasma noradrenaline increased by 38% (p<0.001) and plasma dopamine showed an increase by 58% (p<0.001). Plasma renin concentration increased four-fold during sodium depletion (p<0.001). With combined salt depletion and potassium supplementation, arterial plasma vasopressin decreased by 9.5±4.0 ng/l (p<0.05) compared to control. Urinary excretion of vasopressin together with plasma noradrenaline and dopamine were unchanged during the second week. The reduction of blood pressure was most marked during the first week (143±3/103±2 mmHg, p<0.05), but continued to fall also during the second week. Thus, during sodium restriction in middle-aged hypertensive men, blood pressure reduction occurs concomitantly with inhibited vasopressin release, despite enhanced renin and catecholamine release. Potassium supplementation during sodium restriction induces only minor changes in these variables.