Pharmacokinetics of diclofenac potassium after oral administration of sachets and tablets

There is a host of pharmaceutical formulations of diclofenac, which ensures that it can be used orally, rectally, intrarectally, or topically. Objective - to comparatively analyze the pharmacokinetic parameters and time course of changes in the serum concentration of diclofenac potassium after oral administration in a dose of 50 mg as sachets or sugar-coated tablets. Results. There is evidence that patients tolerate both its sachets and tablets equally well, as confirmed by subjective and objective observations. There are neither marked side effects nor considerable changes in laboratory tests and in the values of vital functions. Diclofenac potassium as early-action tablets (50 and 100 mg) exerts a very good analgesic effect in treating migraine since the plasma concentration of the drug peaks on an average of an hour of administration (range 0,33-2 hours) and the analgesic effect developed following 60-90 min. Conclusion. By comparing the rate of absorption, it may be concluded that diclofenac potassium as sachets will produce a much rapider analgesic effect. Thus, the high solubility of diclofenac potassium and its very good absorbability (as sachets in particular) make the drug a superior analgesic that has a rapid analgesic activity

Ortholog of the polymerase theta helicase domain modulates DNA replication in Trypanosoma cruzi

DNA polymerase theta (Polθ), a member of the DNA polymerase family A, exhibits a polymerase C-terminal domain, a central domain, and an N-terminal helicase domain. Polθ plays important roles in DNA repair via its polymerase domain, regulating genome integrity. In addition, in mammals, Polθ modulates origin firing timing and MCM helicase recruitment to chromatin. In contrast, as a model eukaryote, Trypanosoma cruzi exhibits two individual putative orthologs of Polθ in different genomic loci; one ortholog is homologous to the Polθ C-terminal polymerase domain, and the other is homologous to the Polθ helicase domain, called Polθ-polymerase and Polθ-helicase, respectively. A pull-down assay using the T. cruzi component of the prereplication complex Orc1/Cdc6 as bait captured Polθ-helicase from the nuclear extract. Orc1/Cdc6 and Polθ-helicase directly interacted, and Polθ-helicase presented DNA unwinding and ATPase activities. A T. cruzi strain overexpressing the Polθ-helicase domain exhibited a significantly decreased amount of DNA-bound MCM7 and impaired replication origin firing. Taken together, these data suggest that Polθ-helicase modulates DNA replication by directly interacting with Orc1/Cdc6, which reduces the binding of MCM7 to DNA and thereby impairs the firing of replication origins

High production of pro-inflammatory cytokines by maternal blood mononuclear cells is associated with reduced maternal malaria but increased cord blood infection

BACKGROUND: Increased susceptibility to malaria during pregnancy is not completely understood. Cellular immune responses mediate both pathology and immunity but the effector responses involved in these processes have not been fully characterized. Maternal and fetal cytokine and chemokine responses to malaria at delivery, and their association with pregnancy and childhood outcomes, were investigated in 174 samples from a mother and child cohort from Mozambique. Peripheral and cord mononuclear cells were stimulated with Plasmodium falciparum lysate and secretion of IL-12p70, IFN-gamma, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1beta, TNF, TNF-beta was quantified in culture supernatants by multiplex flow cytometry while cellular mRNA expression of IFN-gamma, TNF, IL-2, IL-4, IL-6, IL-10 and IL-13 was measured by quantitative PCR. RESULTS: Higher concentrations of IL-6 and IL-1beta were associated with a reduced risk of P. falciparum infection in pregnant women (p < 0.049). Pro-inflammatory cytokines IL-6, IL-1beta and TNF strongly correlated among themselves (rho > 0.5, p < 0.001). Higher production of IL-1beta was significantly associated with congenital malaria (p < 0.046) and excessive TNF was associated with peripheral infection and placental lesions (p < 0.044). CONCLUSIONS: Complex network of immuno-pathological cytokine mechanisms in the placental and utero environments showed a potential trade-off between positive and negative effects on mother and newborn susceptibility to infection

Antibiotic prophylaxis in antenatal nonrefluxing hydronephrosis, megaureter and ureterocele

Observation is a conservative management option in infants with nonrefluxing hydronephrosis, primary nonrefluxing megaureter and ureterocele diagnosed postnatally following antenatal detection of hydronephrosis. Antibiotic prophylaxis might be a sensible regimen under these circumstances to prevent UTI in this population who are potentially at increased risk. However, studies examining the efficacy of prophylactic antibiotics are sparse in this setting. For each condition, prophylactic policies seem extremely variable, and UTI rates vary widely with comparable rates reported between patients followed on and off antibiotics. Overall, antibiotic prophylaxis seems unnecessary in patients with isolated low-grade hydronephrosis. Patients with high-grade nonrefluxing hydronephrosis seem at increased risk of UTI, with risk further increasing in patients with associated ureteral dilatation (hydroureteronephrosis) irrespective of the presence of a ureterocele. Obstruction might be an additional independent risk factor, but the diagnosis of obstruction is often possible only in retrospect. The data available suggest that infants are the most at risk of UTI during the first 6 months of life, particularly if they undergo catheterization during workup examinations. Thus, antibiotic prophylaxis might be prudent during the first 6-12 months of life in patients with high-grade hydronephrosis and hydroureteronephrosis with or without ureterocele, and particularly before completion of the diagnostic workup. Paediatric urologists are urged to embark on controlled trials to compare patients followed with and without antibiotic prophylaxis