Does the feeding strategy enhance the aerobic granular sludge stability treating saline effluents?

The development and stability of aerobic granular sludge (AGS) was studied in two Sequencing Batch Reactors (SBRs) treating fish canning wastewater. R1 cycle comprised a fully aerobic reaction phase, while R2 cycle included a plug-flow anaerobic feeding/reaction followed by an aerobic reaction phase. The performance of the AGS reactors was compared treating the same effluents with variable salt concentrations (4.97-13.45 g NaCl/L) and organic loading rates (OLR, 1.80-6.65 kg CODs/(m3·d)). Granulation process was faster in R2 (day 34) than in R1 (day 90), however the granular biomass formed in the fully aerobic configuration was more stable to the variable feeding composition. Thus, in R1 solid retention times (SRT), up to 15.2 days, longer than in R2, up to 5.8 days, were achieved. These long SRTs values helped the retention of nitrifying organisms and provoked the increase of the nitrogen removal efficiency to 80% in R1 while it was approximately of 40% in R2. However, the presence of an anaerobic feeding/reaction phase increased the organic matter removal efficiency in R2 (80-90%) which was higher than in R1 with a fully aerobic phase (75-85%). Furthermore, in R2 glycogen-accumulating organisms (GAOs) dominated inside the granules instead of phosphorous-accumulating organisms (PAOs), suggesting that GAOs resist better the stressful conditions of a variable and high-saline influent. In terms of AGS properties an anaerobic feeding/reaction phase is not beneficial, however it enables the production of a better quality effluent.

Effects of the cycle distribution on the performance of SBRs with aerobic granular biomass.

The aerobic granular systems are mainly sequencing batch reactors where the biomass is submitted to feast-famine regimes to promote its aggregation in the form of granules. In these systems, different cycle distributions can be applied for the simultaneous removal of organic matter, nitrogen and phosphorus. In this work two strategies were followed in order to evaluate the effects of the cycle distribution. In the first experiment, the length of the operational cycle was decreased in order to maximize the treatment capacity and consequently the famine/feast ratio was also decreased. In the second experiment, an initial anoxic phase was implemented to improve nitrogen removal efficiency. The results obtained showed that to reduce the famine/feast ratio from 10 to 5 was possible by increasing the treated organic and nitrogen loading rates in the system to 33%, without affecting the removal efficiencies of organic matter (97%) and nitrogen (64%) and producing a slight detriment of the granules characteristics. On the other hand, the implementation of an anoxic phase of 30 min previous to the aerobic one with a pulse-fed mode increased the nitrogen removal of pig manure from 20 to 60%, while the cycle configuration comprising a continuous feeding simultaneous with an anoxic phase of 60 min did not enhance the nitrogen removal and even worsen the ammonia oxidation.

Daptomycin is effective for treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus epidermidis.

This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 microg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 microg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log(10) CFU/g vegetation [interquartile range {IQR}, 0 to 1 log(10) CFU/g vegetation] versus 2 log(10) CFU/g vegetation [IQR, 2 to 2 log(10) CFU/g vegetation] and 2 log(10) CFU/g vegetation [IQR, 0 to 2.8 log(10) CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log(10) CFU/g vegetation [IQR, 2 to 6 log(10) CFU/g vegetation] versus 7.1 log(10) CFU/g vegetation [IQR, 5.2 to 8.5 log(10) CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

This study evaluated the activity of daptomycin combined with either gentamicin or rifampin against three methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in vitro and one isolate in vivo against a representative strain (MRSA-572). Time-kill experiments showed that daptomycin was bactericidal against these strains at concentrations over the MIC. Daptomycin at sub-MIC concentrations plus gentamicin at 1x and 2x the MIC yielded synergy, while the addition of rifampin at 2 to 4 microg/ml resulted in indifference (two strains) or antagonism (one strain). The in vivo activity of daptomycin (6 mg/kg of body weight once a day) was evaluated +/- gentamicin (1 mg/kg intravenously [i.v.] every 8 h [q8h]) or rifampin (300 mg i.v. q8h) in a rabbit model of infective endocarditis by simulating human pharmacokinetics. Daptomycin plus gentamicin (median, 0 [interquartile range, 0 to 2] log10 CFU/g vegetation) was as effective as daptomycin alone (0 [0 to 2] log10 CFU/g vegetation) in reducing the density of bacteria in valve vegetations (P = 0.83), and both were more effective than daptomycin plus rifampin (3 [2 to 3.5] log10 CFU/g vegetation; P < 0.05) for the strain studied. In addition, daptomycin sterilized a ratio of vegetations that was similar to that of daptomycin plus gentamicin (10/15 [67%] versus 9/15 [60%]; P = 0.7), and both regimens did so more than daptomycin plus rifampin (3/15 [20%]; P = 0.01 and P = 0.02, respectively). No statistical difference was noted between daptomycin plus gentamicin and daptomycin alone for MRSA treatment. In the combination arm, all isolates from vegetations remained susceptible to daptomycin, gentamicin, and rifampin. Sixty-one percent of the isolates (8/13) acquired resistance to rifampin during monotherapy. In the daptomycin arm, resistance was detected in only one case, in which the daptomycin MIC rose to 2 microg/ml among the recovered bacteria. In conclusion, the addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in the treatment of experimental endocarditis due to MRSA.

Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract.

OBJECTIVE: To evaluate the effect of oral administration of selenium and zinc tablets in patients with cancer of the digestive tract during chemotherapy. DESIGN: A case-control, randomized study. SETTING: Medical Oncology, II University of Naples, Naples, Italy. SUBJECTS: A total of 60 patients (median age 55 y, range 46-61 y) with diagnosis of gut cancer were randomized in 1999. Patients were treated for 60 days with chemotherapy. INTERVENTIONS: Trace elements were measured by atomic absorption spectroscopy. The nutritional status of the patients was assessed by biochemical and bio-impedance analysis (BIA) parameters in basal condition and after 60 days of treatment. Oral administration of selenium and zinc in oral tablet form for 50 days was Se 200 microg/day (50 microg/tablet) and Zn 21 mg/day (7 mg/tablet). RESULTS: Both in the basal condition and at 60 days all patients were malnourished. Selenium and zinc concentrations were significantly lower (P < 0.01) whereas copper concentration was significantly higher (P < 0.01) in cancer patients than in control subjects. However, 21/30 (70%) of those treated with Se and Zn did not showed a further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite. On the other hand, 24/30 (80%) untreated patients had a significant decline of all parameters studied after 60 days (prealbumin, cholesterol, transferrin, P < 0.05 vs 0 time; total proteins, albumin/globulin ratio, P < 0.01 vs 0 time; fat-free mass, fat mass, Na+/K+ ratio, body mass index P < 0.05 vs 0 time; fat free mass/fat mass, total body water, extra cellular/intra cellular water, basal metabolic rate: P < 0.01 vs 0 time). CONCLUSIONS: Data indicate that Se and Zn supplementation may improve the clinical course of general conditions in patients with gut cancer. These effects of Se and Zn require confirmation in an independent trial of appropriate design before new public health recommendations regarding Se and Zn supplementation can be made.

Interferon-alpha may exacerbate cryoblobulinemia-related ischemic manifestations: an adverse effect potentially related to its anti-angiogenic activity.

The discovery of the strong association between hepatitis C virus (HCV) infection and the development of mixed cryoglobulinemia has motivated active testing of antiviral-directed alternative therapies. Several trials have demonstrated that classic cryoglobulinemia-associated manifestations improve with interferon-alpha (IFNalpha) treatment. Herein we report on 3 HCV-infected patients with severe cryoglobulinemia-related ischemic manifestations who were closely followed up during IFNalpha therapy. Clinical evaluations with special attention to ischemic lesions, liver function tests, and cryocrit determinations were serially performed. In addition to prednisone and immunosuppressive agents, the patients received IFNalpha at 3 x 10(6) units, 3 times per week for 2 months, 3 months, and 4 months, respectively. In all 3 patients, systemic features improved, liver function results returned to normal, and cryocrit values decreased. However, ischemic lesions became less vascularized and ischemia progressed, leading to transmetatarsal and subcondylar amputation, respectively, in 2 of the patients and fingertip necrosis and ulcer enlargement in the third. Skin biopsies performed before IFNalpha therapy and after 2 months of IFNalpha therapy in the third patient showed a significant decrease in subepidermal microvessels. When IFNalpha was discontinued, the lesions finally healed. Cryoglobulinemia-related ischemic lesions may worsen during IFNalpha treatment, presumably through a decrease in inflammation-induced angiogenesis. The anti-angiogenic activity of IFNalpha may delay the appropriate healing of ischemic lesions.

Actinomycotic splenic abscesses presenting with arthritis.

An 18-month-old Caucasian female began with a high fever. She developed swelling in one finger and one toe. Abdominal ultrasound revealed multiple abscesses in her spleen. Multiple blood culture and splenic abscess aspirations grew no pathogens. She had transient response to multiple antibiotics and splenic abscess drainage, but fever returned along with subcutaneous nodules. Culture of splenic tissue from her second splenic drainage eventually grew one organism identified as Actinomyces naeslundii. Therapy with high dose penicillin followed by amoxicillin p.o. and total splenectomy led to complete recovery.

Isolation of a cDNA encoding human holocarboxylase synthetase by functional complementation of a biotin auxotroph of Escherichia coli.

Holocarboxylase synthetase (HCS) catalyzes the biotinylation of the four biotin-dependent carboxylases in human cells. Patients with HCS deficiency lack activity of all four carboxylases, indicating that a single HCS is targeted to the mitochondria and cytoplasm. We isolated 21 human HCS cDNA clones, in four size classes of 2.0-4.0 kb, by complementation of an Escherichia coli birA mutant defective in biotin ligase. Expression of the cDNA clones promoted biotinylation of the bacterial biotinyl carboxyl carrier protein as well as a carboxyl-terminal fragment of the alpha subunit of human propionyl-CoA carboxylase expressed from a plasmid. The open reading frame encodes a predicted protein of 726 aa and M(r) 80,759. Northern blot analysis revealed the presence of a 5.8-kb major species and 4.0-, 4.5-, and 8.5-kb minor species of poly(A)+ RNA in human tissues. Human HCS shows specific regions of homology with the BirA protein of E. coli and the presumptive biotin ligase of Paracoccus denitrificans. Several forms of HCS mRNA are generated by alternative splicing, and as a result, two mRNA molecules bear different putative translation initiation sites. A sequence upstream of the first translation initiation site encodes a peptide structurally similar to mitochondrial presequences, but it lacks an in-frame ATG codon to direct its translation. We anticipate that alternative splicing most likely mediates the mitochondrial versus cytoplasmic expression, although the elements required for directing the enzyme to the mitochondria remain to be confirmed.

Metabolic effects of strict salt restriction in essential hypertensive patients.

OBJECTIVE: Some observations suggest that a strict low-salt diet may induce unfavourable metabolic side-effects. The main aim of this study was to analyse the possible consequences of severe salt restriction in mildly hypertensive patients. DESIGN: The study was carried out through a randomized double-blind protocol. SUBJECTS: Forty-seven ambulatory patients proceeding from the hypertension unit were initially admitted: 17 were lost, and 30 non-diabetic mildly hypertensives (DBP 90-104 mmHg) with normal renal function completed the protocol. INTERVENTION: After a wash-out period, patients were maintained on a low-salt intake (2.8 +/- 1.0 g day-1 of NaCl) and placebo for 2 weeks, and the same diet and salt supplements (11.7 +/- 2.5 g day-1 of NaCl) for another 2 weeks, separated by a second wash-out period. MEASURES: At the end of each dietary period, blood pressure (BP) and body weight were measured, and a blood sample was taken for determination of routine serum chemistries, plasma lipid and apolipoprotein concentrations, immunoreactive insulin (IRI), and plasma renin activity (PRA). Urinary 24 h excretion of sodium and potassium were measured. RESULTS: During the salt restriction period BP did not change, weight lowered, and PRA raised. There was a significant increase in serum level of creatinine, uric acid, IRI, total cholesterol and apo B, and a decrease in HDL cholesterol and apo A-I. CONCLUSION: As previously suggested, these observations seem to indicate that strict salt restriction may cause, at least in the short-term, adverse metabolic changes in hypertensive patients.

[Effect of moderate salt restriction on the antihypertensive action of nifedipine: a double blind study]. / Influencia de la restricción salina moderada sobre la actividad antihipertensiva de la nifedipina: un estudio doble ciego.

Moderate salt restriction is of debatable efficacy in the treatment of mild or moderate hypertension; however, salt restriction enhances the activity of most antihypertensive drugs. Some observations suggest that the antihypertensive activity of calcium antagonists is not increased or could even decrease with dietary salt restriction. In the present work 15 patients suffering arterial hypertension and normal renal function are studied during four two week periods; a) unrestricted diet and medication, b) unrestricted diet and nifedipine (40 mg/day), c) low salt diet (5 g of salt/day) and nifedipine, and d) the same low salt diet, nifedipine and a salt supplement (6 g/day); salt or placebo were given in a double blind manner. At the end of each period arterial blood pressure was recorded, a urine sample for sodium determination was taken, and a blood sample was drawn for serum renine activity and biochemical parameters; at the end of each period patients' weight was recorded. Blood pressure significantly decreased (systolic: 9.83%, and dyastolic 11.17%) in patients treated with nifedipine, with no differences observed with salt modifications. Urinary sodium reflected correctly dietary salt modifications. Serum renine activity significantly increased during salt restriction. No significant changes were observed in weight or in the biochemical parameters studied. These results seem to suggest that the antihypertensive effect of nifedipine in patents suffering mild to moderate essential hypertension, with no change observed is not altered by the amount of salt in diet, at least within the limits studied (89.7 to 190 mEq/day of Sodium).

Metacarpal cortical thickness in uremic patients on regular hemodialysis.

Metacarpal cortical thickness was measured in 83 patients with chronic renal failure undergoing periodic hemodialysis. Patients were dialyzed twice weekly, 8--9h per session, with a calcium concentration in dialysate of 6.5 mg/dl. Supplements of calcium, vitamin D (5,000 I.U. a day), steroid anabolic hormones, and aluminium hydroxyde were administered to all patients. They were on a normal protein intake and unrestricted physical activity. The results show that the young males have a reduction in cortical thickness as compared to age-matched controls, and that there is a progressive loss in cortical width as the length of dialysis increases. This bone loss is statistically significant in males during their first 18 months of dialysis.