Evaluation of factors influencing the trace metals in Puducherry and Diu coasts of India through multivariate techniques.

In recent years, urban and industrial development initiatives at Puducherry and Diu such as tourism, shipping, and fisheries have led to sediment contamination by trace metals, and contributed to this investigation that extended from 2016 to 2017. Strong factor loadings of Cd (0.94), Ni (0.84), Al (0.84), Cr (0.83), Co (0.82), and Fe (0.78) illustrated the variability at Puducherry, whereas Cr (0.88), Cd (0.86), Ni (0.83), Co (0.77), Cu (0.77), and Fe (0.77) showed variability at Diu. The mean rank order distribution of the top three metals in sediment was Fe > Al > Mn, which exhibited higher variability. The highest contamination factor was observed for Cd at Diu, whereas the lowest was observed at Puducherry for Al. Similarly, the risk index also exhibited considerable risk which could be attributed to Cd contamination in the sediment at Diu compared with that at Puducherry. The results obtained are essential to establish a reference for better comparison and management of the tropical environments.

Assessment of ecological health of Swarnamukhi river estuary, southeast coast of India, through AMBI indices and multivariate tools.

A combination of biotic indices, geo-accumulation (Igeo) index, and a multivariate approach were applied to assess the anthropogenic influence on the benthic community at five stations from 2018 to 2019 in the Swarnamukhi river estuary, Nellore, India. Non-metric multidimensional scaling and cluster analysis indicated that the Buckingham canal (BC) station showed azoic conditions and formed a separate cluster. Strong positive factor loadings of Cd (0.96), Al (0.93), Zn (0.91), Fe (0.90), Co (0.89), Cu (0.89), Ni (0.87), Pb (0.85), Cr (0.77), organic matter (0.94), Silt (0.92), and clay (0.93) and negative loading of sand (-0.90) showed the variability in sediment. AMBI results illustrated the disturbance status of each station and classified BC station as 'extremely disturbed' class, and M-AMBI assessed the ecological status as 'bad'. The Igeo index also revealed metal (Cd) contamination. The present study illustrated that the combined approach is effective for ecological assessment of coastal ecosystem.

Evaluation of trace metals in seawater, sediments, and bivalves of Nellore, southeast coast of India, by using multivariate and ecological tool.

Urbanization in recent years has driven us to investigate metal contamination on Nellore coast by collecting seawater, sediment, and bivalve samples monthly at five stations from 2015 to 2017. Non-metric multidimensional scaling and cluster analysis indicated that open sea (OS) samples were markedly different from the samples collected at other stations. Strong factor loadings of Al (0.76), Mn (0.79), and Cd (0.78) showed variability in seawater, while those for Fe (0.76), Ni (0.77), Zn (0.85), and Pb (0.81) showed variability in sediment. The mean values of Fe (346 ppm) and Mn (21 ppm) were high in bivalves compared to the mean values of other metals. A higher contamination factor was observed for Cd at Buckingham Canal, while the lowest was observed for sediment in OS. The order of trace metals in sediments according to risk index was Cd > Pb > Cu > Cr > Zn. The results obtained are essential to establish a reference for better comparison of tropical environments.

Temperature tolerance of some estuarine fishes.

The temperature tolerance of estuarine fishes Etroplus suratensis (Bloch), Therapon jarbua (Forsskal), Ambassis commersoni (Cuvier) collected from Vellar estuary, South India in 1986-87 were determined in the laboratory. E. suratensis and T. jarbua were found to be more tolerant to a wide range of temperature (16.5-41.5 degrees C for E. suratensis and 13.5-40.6 degrees C for T. jarbua), A. commersoni could tolerate from 15.5 to 38.5 degrees C. The tolerance area was found to be 512 units in E. suratensis, 629 units in T. jarbua and 442 units in A. commersoni. Among the fishes tested T. jarbua had a high tolerance area (629 units) than other fishes tested. It is evident from the results that 15 degrees C increase in acclimation temperature cause a shift of 4.02 degrees C (E. suratensis) and 3.05 degrees C (T. jarbua and A. commersoni) in upper incipient lethal temperature.

Initial and steady state pharmacokinetics of cilazapril in congestive cardiac failure.

Twenty one patients with NYHA class II-III congestive heart failure received single ascending doses of 0.5, 1.25 and 2.5 mg cilazapril daily followed by the minimum effective dose for six weeks. Fifteen patients completed the study, but the data from only 11 were sufficiently complete for kinetic evaluation. The pharmacokinetics of the metabolite, cilazaprilat, after a single dose of 0.5 mg cilazapril were similar to previous observations in healthy volunteers at identical dosage. Repeat administration, however, led to greater accumulation than previously observed in volunteers at the higher dosages of 1.25 or 5 mg given for 8 days. Seven patients experienced adverse events. Four were severe, leading to withdrawal of the patients from the study, but only one event was related to cilazapril. Of the other three, one suffered a myocardial infarction and subsequently died due to worsening congestive heart failure. One other patient was withdrawn with two adverse events probably related to cilazapril. No other deaths occurred amongst the study population, and there were no significant abnormalities in haematology or blood chemistry.

Pharmacokinetics of cilazapril during repeated oral dosing in healthy young volunteers.

The pharmacokinetics of cilazapril and its active metabolite cilazaprilat in plasma were investigated in an open study of 13 healthy male volunteers, aged 18 to 43 years. One capsule containing 2.5 mg cilazapril was administered to each volunteer daily for 8 days. Plasma samples were obtained after the first and eighth doses. Concentrations of cilazapril, cilazaprilat and activities of angiotensin converting enzyme (ACE) were measured by radioenzymatic methods. For cilazapril, the values of apparent plasma clearance (about 15 l/h) and volume of distribution (around 28 l) were sufficiently high to suggest that significant pre-systemic hydrolysis to cilazaprilat occurred. There were no significant changes in these values after repeated dosing. There were small, but statistically significant, increases in mean peak concentrations, mean areas under concentration-time curves and mean trough concentrations from the first to the eighth dose. A steady state was achieved after eight doses with an accumulation of 20-30%. The mean effective half-life was approximately 9 h. Despite the accumulation of cilazaprilat in plasma, there were no significant differences in plasma ACE inhibition from the first to the eighth dose.

The pharmacokinetics and bioavailability of cilazapril in normal man.

1. The pharmacokinetics of cilazapril and its active metabolite, cilazaprilat, were investigated in a three-part crossover study in 12 healthy male volunteers aged 19-38 years, excluding one subject who withdrew from the study. 2. Single 2.5 mg oral doses of cilazapril, and equivalent oral and intravenous doses of cilazaprilat were administered as aqueous solutions to the fasted subjects. There was an interval of 1 week between treatments. Concentrations of cilazapril and cilazaprilat in plasma and urine, and activities of angiotensin converting enzyme (ACE) in plasma were measured by radioenzymatic methods. 3. After 10 min infusion of cilazaprilat, the mean plasma concentration was 194 ng ml-1, and ACE inhibition was almost 100%. The decline in concentrations was polyphasic, with mean half-lives for the periods 1-4 h and 24-168 h of 0.90 and 46 h, respectively. Between 4 and 24 h the decline was non-linear, and ACE inhibition decreased from 91% to 67%. Urinary recovery of cilazaprilat averaged 91% of dose. 4. After oral cilazapril, the parent drug was rapidly absorbed and rapidly eliminated, with a mean maximum plasma concentration of 82 ng ml-1 at 0.83 h and a single elimination half-life of 1.3 h. Cilazaprilat peaked at 36 ng ml-1 about 1.7 h after dosing and the decline in concentrations was biphasic, with half-lives of 1.8 h and 45 h. After oral cilazaprilat, plasma concentrations were considerably lower, and the peak later (2.2 h). 5. Urinary recovery data indicated an absolute bioavailability for cilazaprilat of 57% (range 45-75%) from oral cilazapril, but only 19% (range 8-40%) from oral cilazaprilat.(ABSTRACT TRUNCATED AT 250 WORDS)

A pharmacokinetic study of cilazapril in elderly and young volunteers.

1. Cilazaprilat is an inhibitor of angiotensin converting enzyme (ACE) and is the active metabolite of cilazapril. The pharmacokinetics of cilazaprilat, and the inhibition of plasma ACE were investigated in 12 elderly and 12 young healthy volunteers. 2. Single oral 1 mg doses of cilazapril were given to the elderly (age range 65-83 years) and the young (age range 18-31 years) in an open study. Plasma and urinary cilazaprilat concentrations, and plasma ACE activities were measured up to 72 h after dosing by radioenzymatic methods. 3. Cilazapril was well tolerated in both young and elderly subjects. Small falls in blood pressure were observed up to 8-24 h after dosing. 4. The mean peak plasma cilazaprilat concentration in the elderly (11.5 ng ml-1) was significantly greater (P less than 0.02) than the corresponding value in the young (8.3 ng ml-1). Total and renal clearances were significantly lower (both P less than 0.05) in the elderly (12.8 and 5.11 h-1) than in the young (16.0 and 7.21 h-1). Total urinary recovery of cilazaprilat was similar for the two groups at about 43% of dose. 5. Plasma ACE inhibition was slightly greater in the elderly but the mean inhibition in the two groups did not differ by more than 10% at any time-point from 1-72 h. 6. The plasma concentrations of cilazaprilat required for 90% ACE inhibition were similar at 4.7 and 4.8 ng ml-1 in the elderly and young respectively. 7. It is concluded that the age-related changes in cilazaprilat kinetics and in the degree of ACE inhibition are small.(ABSTRACT TRUNCATED AT 250 WORDS)

A pharmacokinetic study of cilazapril in patients with congestive heart failure.

1. The pharmacokinetics of cilazapril and the inhibition of angiotensin converting enzyme (ACE) were investigated in 10 patients with congestive heart failure, NYHA class II-III, receiving diuretics with or without digoxin. 2. Patients received 0.5 mg and 1 mg cilazapril on the first 2 days, followed by 0.5 mg or 1 mg daily for the next 8 weeks, in a single-blind study. Plasma cilazaprilat concentrations and plasma ACE activities were measured by radioenzymatic methods up to 24 h after the first and last doses. 3. After the initial 0.5 mg dose of cilazapril, a mean maximum plasma concentration of cilazaprilat of 6.8 ng ml-1 was observed at 2.3 h. Concentrations declined up to 8 h with a mean half-life of 5.8 h, followed by slower decrease to 24 h. Total clearance, based on data to 24 h, was estimated at 8.5 l h-1, with three-fold inter-individual variation. Mean maximum plasma ACE inhibition was 87%, decreasing to 65% at 24 h. 4. In the multiple dose phase of the study, four patients received cilazapril 0.5 mg daily, and six patients 1 mg daily. Cilazapril accumulation for the 0.5 mg group averaged 77%, but steady state concentrations for the 1 mg group were less than double those of the 0.5 mg group. ACE inhibition profiles at steady state were similar for both groups, and they differed from first dose data only in a somewhat lower inhibition at 24 h. 5. Historical comparison of the first-dose data with those for healthy young volunteers at identical dosage revealed only minor differences in kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)