Hydrops fetalis is a serious condition indicating a bad prognosis of affected fetuses. Incidence of immune hydropsfetalis is significantly decreasing, whereas more and more non-immune hydropsfetalisis are identified. We described a case of the most difficult manifestation of hemolytic disease of a newborn due to rhesus incompatibility. Immune hydrops fetalis occurred due to inadequate immune prophylaxis. While treating the newborn, we applied exchange transfusion, additional transfusion and immunoglobulin therapy. With sensitized pregnant patients, it is necessary to regularly monitor the condition of fetus and titer of mother's antibodies. Considering a difficulty of affected fetuses' disease, it is necessary to strengthen preventive measures by application of rhesus immunoglobulin with affected Rh negative mothers.

Despite remarkable progress in survival of children with acute lymphoblastic leukemia (ALL) which has reached about 85%, early toxicity and relapse rate remain issues that need to to be resolved. Genetic variants are important factors influencing the metabolism of cytotoxic drugs in ALL treatment. Variants in genes coding for methotrexate (MTX)-metabolizing enzymes are under constant scientific interest due to their potential impact on drug toxicity and relapse rate. We investigated methylenetetrahydrofolate reductase (MTHFR) c.677C>T and MTHFR c.1298A>C variants as pharmacogenetic markers of MTX toxicity and predictors of relapse. The study enrolled 161 children with ALL, treated according to the current International Berlin-Frankfurt-Munster group (BFM) for diagnostics and treatment of leukemia and lymphoma protocols. Genotyping was performed using PCR-RFLP and allele-specific PCR assays. Our results revealed similar distributions of MTHFR c.677C>T and MTHFR c.1298A>C genotypes among 104 healthy individuals as compared to pediatric ALL patients. A lower incidence of early MTX toxicity was noted in the MTHFR c.677TT genotype (p=0.017), while MTHFR c.1298A>C genotypes were not associated with MTX toxicity. Carriers of any MTHFR c.677C>T and MTHFR c.1298A>C genotypes did not experience decreased overall survival (OAS) or higher relapse rates. Genetic variants in the MTHFR gene are not involved in leukemogenesis in pediatric ALL. The presence of the MTHFR c.677TT genotype was recognized as a predictive factor for decreased MTX toxicity during the intensification phase of therapy. Neither MTHFR c.677C>T nor MTHFR c.1298A>C genotypes correlated with an increased number of toxic deaths or relapse rate. Our study emphasizes the importance of implementing pharmacogenetic markers in order to optimize pediatric ALL therapy.

Activities of Proximal Tubule Enzymes In Urine of Patients Treated With Gentamicin The activities of the enzymes dominantly localized within the proximal tubules, such as alanine aminopeptidase (AAP), gamma-glutamyl transferase (GGT) and Nacetyl-beta-D-glucosaminidase (NAG), were measured in 12-h urine samples of patients suffering from Gram-negative infections and i.v. treated with gentamicin with the aim of determining the nephrotoxicity of this aminoglycoside antibiotic. The examined groups consisted of 3 - 10 years old children of both sexes, gentamicin-treated, and the control group, each including 30 patients. Urine samples were collected and analyzed five days before the gentamicin application and during the following 10 days of gentamicin treatment (a single i.v. injection per day in the dose of 2.5 mg/kg b.w.). Significant differences in the AAP and GGT activities expressed in U/mmol creatinine were observed between the gentamicin-treated group and the controls already on day 2 (p < 0.05) of the treatment, as well as in the activity of NAG on day 8 (p < 0.01) of the therapy. From these results it can be concluded that even standard gentamicin doses expressed nephrotoxic effects. Statistically significantly increased AAP and GGT activities in the gentamicin-treated group of children recorded already on the 2nd day of treatment demonstrate that these two enzymes represent extremely sensitive indicators of nephrotoxicity. On the other hand, statistically significantly increased NAG activity observed in the gentamicin-receiving group points to more severe gentamicin-provoked injuries of proximal tubules.

Kratak sadr`aj: Radi utvr|ivanja nefrotoksi~nosti aminoglikozidnog antibiotika gentamicina odre|iva na je aktivnost enzi ma dominantno lokalizovanih u proksimalnim tubulama, alaninaminopeptidaze (AAP), g-glutamil-transferaze (GGT) i N-acetil-ß-D-glukozaminidaze (NAG). Odre|ivanje je vr{eno u uzorcima 12-~asovnog urina 30 ispitanika kojima je zbog Gram-negativnih infekcija intravenski apliciran gentamicin u dozama od 5,0 mg/kg telesne mase dnevno. Aktivnosti istih enzima su odre|ivane i u 12-~asovnom urinu 30 ispitanika kontrolne grupe. Polnu strukturu grupa su ~inili ispitanici oba pola i uzrasta neonatalnog perioda. Posle petodnevnog perioda pre tretiranja, eksperimentalna grupa je dobijala gentamicin tokom 10 dana. Statisti~ki zna~ajne razlike u aktivnostima AAP i GGT, izra`ene u U/mmol kreatinina, utvr|ene su izme|u ispitanika eksperimentalne i ispitanika kontrolne grupe osmog dana (p<0,01) sprovo|enja terapije. Aktivnosti NAG kod ispitanika eksperimentalne grupe u odnosu na ispitanike kontrolne grupe se nisu zna~ajno menjale tokom desetodnevnog vremena sprovo|enja terapije. Mo`e se zaklju~iti da desetodnevni tretman ispitanika u neonatalnom periodu uobiajenim dozama gentamicina izaziva blage nefrotoksi ~ne promene koje su pra}ene porastom aktivnosti AAP i GGT, veoma osetljivih indikatora nefrotoksi~nosti, tek pri kraju sprovo|enja terapije. Za isto vreme sprovo|enja terapije nije do{lo do porasta aktivnosti NAG, {to zna~i da nema te`ih o{te}enja }elija proksimalnih tubula na nivou }elijskih organela.Klju~ne re~i: alaninaminopeptidaza (AAP), g-glutamiltrans feraza (GGT), N-acetil-b-D-glukozaminidaza (NAG), urin, gentamicin, neonatalni period Summary: In order to determine the nephrotoxicity of gentamicin, an aminoglycoside antibiotic, activity of the enzymes dominantly localized in proximal tubules, i.e. alanine aminopeptidase (AAP), g-glutamyl transferase (GGT) and N-ace tyl-ß-D-glucosaminidase (NAG) was examined. Deter mina tions were performed in 12-h urine samples of 30 neonates i.v. receiving gentamicin against Gram negative infections in daily doses of 5.0 mg/kg body mass for 10 consecutive days. The activities of the same enzymes were measured in 12-h urine samples of 30 examinées of the control group. The groups consisted of neonates of both sexes. The pretreatment period lasted for 5 days. On day 8 of gentamicin application, statistically significant differences in the activity of AAP and GGT expressed in U/mmol creatinine between the gentamicin-receiving and control group (p<0.01) were found. No significant differences in NAG activity of the gentamicin-treated group in comparison with the control were recorded during the 10-day gentamicin therapy. It can be concluded that 10-day treatment of neonates with usually prescribed gentamicin doses results in mild nephrotoxic changes close to the end of the therapy accompanied by increased activity of both urinary AAP and GGT, known as very sensitive indicators of nephrotoxicity. During the same treatment period no changes in NAG activity were observed, mea...

Kratak sadr`aj: Radi odre|ivanja nefrotoksi~nosti cefalosporinskog antibiotika cefaleksina, pra}ena je aktivnost enzi ma dominantno lokalizovanih u }elijama epitela proksimalnih tubula, alaninaminopeptidaze (AAP), gama-glutamil-transferaze (GGT) i N-acetil-beta-D-glukozaminidaze (NAG). Odre|ivanje aktivnosti enzima je vr{eno u uzorcima 12-~asovnog urina kod 30 ispitanika kojima je, zbog grampozitivnih infekcija respiratornog i urinarnog trakta, per os apliciran cefaleksin u dozama od 50 mg/kg telesne mase dnevno za vreme sprovo|enja terapije do 15 dana. Aktivnosti istih enzima su odre|ivane i u 12-~asovnom urinu 30 ispitanika kontrolne grupe. I eksperimentalna i kontrolna grupa sastojale su se od ispitanika oba pola, starosti od 3 do 10 godina. Statisti~ki zna~ajne razlike u aktivnostima AAP i GGT, izra`ene u U/mmol kreatinina, registrovane su izme |u ispitanika eksperimentalne i ispitanika kontrolne grupe nakon dvanaestog dana sprovo|enja terapije (p < 0,01). Aktiv nost NAG ispitanika eksperimentalne grupe u odnosu na ispitanike kontrolne grupe se nisu zna~ajno menjale zã itavo vreme petnaestodnevne terapije. Mo`e da se za klju~i da petnaestodnevni tretman ispitanika staro sti od 3 do 10 godina preporu~enim dozama cefa leksina izaziva blage nefrotoksi~ne promene pri kraju terapije koje su pra}ene porastom aktivnosti AAP i GGT, veoma osetlji vih indikatora nefrotoksi~nosti. Za ~itavo vreme sprovo|e nja terapije nije do{lo do porasta aktivnosti lizozomalnog enzim a NAG, {to zna~i da ne dolazi do te`ih o{te}enja }elija epitela proksimalnih tubula na nivou organela. The same enzymes were determined in the 12-h urine samples of the corresponding control. Both the control and the expe ri mental group consisted of 30 examinees of both sexes, age range 3-10 years. Sta tistically significant differences in AAP and GGT activities expressed as U/mmol creatinine were recorded after 12 days of cephalexin therapy in comparison with the control (p < 0.01). At the same time, no significant differences in NAG activity of the patients in relation to the control were observed during the entire course of the therapy. Based on the obtained results it can be concluded that treatment of 3-10 years old patients with the applied cephalexin doses for 15 days results in mild nephrotoxic changes close to the end of therapy accompanied by incre ased activities of AAP and GGT, the enzymes known as very sen sitive indicators of nephrotoxicity. The results showing that during the entire period of cephalexin appli cation no changes in NAG, as a lysosomal enzyme, were observed, could be taken as a proof that this antibiotic did not lead to severe injuries of epithelial proximal tubule cells at the level of cell organelles.