Factors that affect concentrations of cyclosporine during the induction period of kidney transplantation: multivariate analysis.

OBJECTIVE: The pharmacokinetics of cyclosporine (CsA) depend on numerous factors over the transplantation course. The aim of this study was to evaluate the impact of several clinical variables on CsA concentrations during the induction period after kidney transplantation. METHODS: Potential variables were contrasted with CsA concentrations at 2 hours postdose (C(2)) and with the area under the concentration curve of CsA (AUC) at days 3 and 10 after transplantation. Evaluated variables were: recipient age, gender, body mass index (BMI), type/duration of previous dialysis, pretransplant serum creatinine (sCr), donor type, CsA dose, cold ischemia time, reduction of sCr, and use of other immunosuppressive drugs. RESULTS: This series included 112 patients who displayed an average age of 43 ± 13 years, including 62 men and 31 recipients of living donor organs. The induction dose of CsA was 8.36 ± 1.53 mg/kg. On day 3, the C(2) was related to the reduction of sCr (P = 0.034) and to the BMI (P = 0.033). There was an inverse correlation with pretransplant sCr (P = 0.012). The AUC correlated with BMI (P = 0.027) and living donor category (P = .002). Patients receiving rapamycin or a locally procured kidney showed a trend toward higher AUC values. On day 10, the CsA dose and use of rapamycin showed a trend to higher values of C(2); the AUC was related to the CsA dose (P = .034). None of the other variables showed significant effects. Analysis between variables showed that time on dialysis correlated with the pretransplant sCr (P = .002) and that the CsA dose was negatively associated with BMI (P = .009). CONCLUSION: Pretransplant sCr, BMI, living donor kidney category, better functional recovery, and the dose of CsA were predictors of CsA concentrations of clinical interest during this induction period. The effect of BMI was not related to higher doses of CsA.

Prophylaxis and treatment of Chagas disease in renal transplant donor and recipient: case report.

Chagas disease is a prevalent zoonosis in Latin America, caused by the protozoa Trypanosoma cruzi and transmitted by Triatoma infestans. Part of the infectious cycle consists of chronic subclinical parasitemia, causing in the long term end-organ damage. Amastigotes have been isolated from various organs including native and allograft renal parenchyma; thus, transplantation plus immunosuppression therapy is another mode of disease transmission and reactivation. Herein, we report 2 successful kidney transplantations cases in which either infection or reactivation was averted using prophylactic nitroderivates.

Strategies for prevention of cytomegalovirus infection in renal transplant patients.

OBJECTIVE: Cytomegalovirus (CMV) constitutes the principal viral infection in renal transplant patients. The indirect consequences of CMV infection increase the risks for acute and chronic rejection, secondary infections, lymphoproliferative disorders, atherosclerosis, and cardiovascular deaths. The direct effects depend on the affected organ. There have been strategies to prevent CMV disease: prophylaxis and preemptive strategy. The aim of this study was to compare the incidences of disease and infection due to CMV among our patients. PATIENTS AND METHODS: We performed a retrospective analysis of all our renal transplant patients between January 2000 and January 2008. RESULTS: Four groups were identified among 94 patients: without any preventive strategy; brief prophylaxis; formal prophylaxis; and preemptive treatment. There were no significant differences among the groups in the incidences of CMV disease, acute renal rejection, or survival. The greatest number of infections was registered in the group with brief prophylaxis (P = .006); 50% of the registered infections occurred before 150 days posttransplantation. CONCLUSIONS: We concluded that the preemptive strategy is appropriate for the low-risk patient, while prevention with antiviral drugs should be reserved for intermediate- and high-risk patients. A brief treatment for prevention is an alternative to prevent CMV disease, but it needs to be followed with serial, long-term evaluation of antigenemia for >150 days posttransplantation.

Determinación de los niveles de ácido linoleico conjugado (ALC) en alimentos lácteos en Chile / Amounts of conjugate linoleic acid (ALC) in lacteal foods in Chile

Se midieron las cantidades de acido linoleico conjugado (ALC) - isómeros: cis-9, trans-11, trans-10, cis-12 y cis-10, cis-12 -en leche de estanque de la empresa NESTLE y de alimentos lácteos en Chile, mediante cromatografía de gas. El ALC encontrado fue más alto (p < 0.05) en las muestras tomadas en la ciudad de Osorno comparado con la leche de la ciudad de Los Angeles. A nivel estacional el valor más alto de ALC de leche líquida fue encontrado durante la primavera en la ciudad Osorno (1,72 g/100g), mientras que el valor más bajo se presentó en invierno (0,415 g/100g) en la ciudad de Los Angeles. La cantidad promedio de ALC en leche en polvo y de leche condensada fue de 1,967 y 1,493 g/100g respectivamente durante el año 2004. La mantequilla, el queso y la crema presentaron promedios de 1,502,0,883 y 1,900 g/ lOOg respectivamente de ALC. Se concluye que los productos lácteos analizados tienen altos valores de ALC en Chile.

The amounts of conjugated linoleic acid (ALC) - homers: cis-9, trans-11, trans-10, cis-12 and cis-10, cis-12- were measured in a milk tank of the NESTLE Company and of diary food in Chile and were analyzed through gas chromatography. The ALC was found higher (p <0.05) in samples taken in the city of Osorno compared to milk of the city of Los Angeles. The highest value was found during spring in Osorno (1,72 g/100 g), while the lowest value (0,415 g/100 g) was found in winter in Los Angeles. The average amount of ALC in milk powder and condensed milk was of 1,967 and 1,493 g/100 g, respectively, during 2004. Butter, cheese and cream had respectively an average of 1,502, 0,883 and 1,900 g/100 g. In conclusion, the diary products analyzed have a high value of ALC in Chile.

Abbreviated AUC monitoring of cyclosporine more adequately identified patients at risk for acute rejection during induction of immunosuppressive therapy after kidney transplantation than recommended C2 concentration values.

OBJECTIVE: Monitoring of cyclosporine (CsA) is critical during the induction of immunosuppressive therapy. Although most centers have incorporated C2 levels, our unit still uses an abbreviated AUC model which includes concentrations at C1, C2, and C6 post-dose (AUC(1-6)). The objective of this study was to compare both strategies of CsA monitoring during the first 30 days after kidney transplantation. PATIENTS AND METHODS: The study included 89 recipients induced with CsA microemulsion and steroids. AUC(1-6) profiles were performed around days 3, 10, and 30 after transplantation with a target of 5500 to 6000 ng*h/mL considered therapeutic. For comparison purposes, a value of C2 >/= 1500 ng/mL was also considered therapeutic. Mean C2 and AUC(1-6) values were low dated with biopsy-proven acute rejection episodes (BPAR) during the study period. RESULTS: Twenty patients received living donor kidneys and overall there were 46 females. During this period, 253 AUC(1-6) were performed including 44 (17.4%) below the therapeutic range. When the analysis included only C2, 171 (67.6%) were below the therapeutic target (P < .001). Five patients experience BPAR and only AUC(1-6) at day 10 discriminated rejectors versus nonrejectors (5645 +/- 1390 and 8221 +/- 2502, respectively; P = .008). C2 was not significantly different at any time in either group. CONCLUSIONS: In this study, abbreviated AUC monitoring more adequately identified patients at risk for acute rejection than C2. Recommended C2 concentration levels need to be redefined in our patients.

Identification and characterization of putative virulence genes and gene clusters in Aeromonas hydrophila PPD134/91.

Aeromonas hydrophila is a gram-negative opportunistic pathogen of animals and humans. The pathogenesis of A. hydrophila is multifactorial. Genomic subtraction and markers of genomic islands (GIs) were used to identify putative virulence genes in A. hydrophila PPD134/91. Two rounds of genomic subtraction led to the identification of 22 unique DNA fragments encoding 19 putative virulence factors and seven new open reading frames, which are commonly present in the eight virulence strains examined. In addition, four GIs were found, including O-antigen, capsule, phage-associated, and type III secretion system (TTSS) gene clusters. These putative virulence genes and gene clusters were positioned on a physical map of A. hydrophila PPD134/91 to determine their genetic organization in this bacterium. Further in vivo study of insertion and deletion mutants showed that the TTSS may be one of the important virulence factors in A. hydrophila pathogenesis. Furthermore, deletions of multiple virulence factors such as S-layer, serine protease, and metalloprotease also increased the 50% lethal dose to the same level as the TTSS mutation (about 1 log) in a blue gourami infection model. This observation sheds light on the multifactorial and concerted nature of pathogenicity in A. hydrophila. The large number of putative virulence genes identified in this study will form the basis for further investigation of this emerging pathogen and help to develop effective vaccines, diagnostics, and novel therapeutics.

A type III secretion system is required for Aeromonas hydrophila AH-1 pathogenesis.

Aeromonas hydrophila is a gram-negative opportunistic pathogen in fish and humans. Many bacterial pathogens of animals and plants have been shown to inject anti-host virulence determinants into the hosts via a type III secretion system (TTSS). Degenerate primers based on lcrD family genes that are present in every known TTSS allowed us to locate the TTSS gene cluster in A. hydrophila AH-1. A series of genome walking steps helped in the identification of 25 open reading frames that encode proteins homologous to those in TTSSs in other bacteria. PCR-based analysis showed the presence of lcrD homologs (ascV) in all of the 33 strains of A. hydrophila isolated from various sources. Insertional inactivation of two of the TTSS genes (aopB and aopD) led to decreased cytotoxicity in carp epithelial cells, increased phagocytosis, and reduced virulence in blue gourami. These results show that a TTSS is required for A. hydrophila pathogenesis. This is the first report of sequencing and characterization of TTSS gene clusters from A. hydrophila. The TTSS identified here may help in developing suitable vaccines as well as in further understanding of the pathogenesis of A. hydrophila.

Introducción de micofenolato asociado a suspensión o reducción de la ciclosporina en trasplante renal: evaluación de una estrategia para el manejo de la nefropatía crónica del injerto / Effects of the administration of micofenolate mofetil associated to suspension or reduction of the cyclosporin in kidney transplant: evaluation of a management strategy of the chronic graft nephropathy

Esta revisión incluyó seis pacientes trasplantados, en tratamiento con CyA (Neoral) y Prednisona, con diagnóstico clínico de NCI caracterizado por un alza progresiva de la creatinina plasmática, y en cuatro de ellos estudio histológico concordante. MM se incorporó en un lapso no inferior a seis semanas, período en el cual se redujo y/o suspendió la CyA. La función renal y las complicaciones del tratamiento se evaluaron semanalmente en este período y en forma mensual hasta los 24 meses. La introducción de MM se efectuó en promedio a los 66 meses post-trasplante (rango 12 a 240 meses). Durante los 24 meses de seguimiento, se observó una tendencia progresiva a disminuir los niveles de creatinina. Sin embargo, esta diferencia no fue estadísticamente significativa. Durante este período no se observó ningún episodio de rechazo agudo o eventos adversos mayores. Sólo un paciente presentó toxicidad gastrointestinal, secundaria al uso de MM. La adición de MM acompañado de reducción o suspensión de CyA, en este grupo de pacientes con NCI, permitió mantener estables los niveles de creatinina durante el período en estudio, disminuyendo aparentemente la progresión de la enfermedad. La conversión demostró ser segura.

A double-stranded RNA mycovirus in Botrytis cinerea.

In wild-type Botrytis cinerea CVg25 strain we have detected the presence of extrachromosomal genetic elements corresponding to double-stranded RNA molecules. These genetic elements have been designated L, M1 and M2 with molecular sizes of 8.3, 2.0 and 1.4 kb, respectively. The visualization by electron microscopy of mycelium ultrathin sections from B. cinerea CVg25 showed the presence of isometric virus-like particles of about 40 nm in diameter. Linear sucrose gradient centrifugation of mycelium-free extracts was done to determine if the double-stranded RNAs were associated with virus-like particles. The gradient profile obtained at 260 and 280 nm revealed a major peak that was analyzed by both agarose-gel electrophoresis and electron microscopy. It was observed that only the L-double-stranded RNA molecule copurified with isometric virus-like particles. These virus-like particles had a similar morphology and size as those detected by electron microscopy in the mycelium sections. These results suggest that only the L-double-stranded RNA would be encapsidated.

[Cutaneous response to 2 and 10 units of tuberculin in infants]. / Respuesta cutánea de lactantes a 2 y 10 unidades de tuberculina.

A study was done in 322 healthy, well nourished infants, 3 to 18 months old from day care centers of metropolitan Santiago, Chile, that were given BCG immunization in their neonatal period: 304 (94.4%) of them showed BCG scars and were included in a double blind open study, to determine the cutaneous responses to 2 TU and 10 TU tuberculin (PPD). There were no differences in the mean size of cutaneous reactions nor in percent positive responses (greater than or equal to 10 mm), but cutaneous reactions greater than or equal to 15 mm were more frequent in infants tested with PPD 10 TU. In 184 out of 304 infants (60.5%) tuberculin reactions were negative (less than or equal to 10 mm). Eighteen out of 322 infants (5.6%) that didn't show BCG scars were injected with PPD 2 TU: tuberculin reactions sized 6 to 9 mm were recorded in 3/18 of these infants but none of them attained 10 mm. Fifty five infants whose tuberculin reactions were 5 mm or less were retested: a booster effect was likely from the appearance of enhanced dermal response after a second tuberculin test done with the same or higher tuberculin strength than the first one in 12/47 of these infants with BCG scar (25%) and in only 1/8 such subjects without BCG scar.