Investigation of the Hydrolytic Stability of the HLDF-6-AA Antitumor Peptide by the Method of Accelerated Aging

Russian Journal of Bioorganic Chemistry - The HLDF-6 hexapeptide corresponded to the 41–46 (TGENHR) fragment of the Human Leukemia Differentiation Factor (HLDF) and exhibited a wide spectrum...     

The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.     

Pharmacokinetics of HLDF-6-AA Peptide in the Organism of Experimental Animals

Russian Journal of Bioorganic Chemistry - Pharmacokinetics of the promising antitumor peptide HLDF-6-AA (Ac-ThrGlyGluAsnHisArg-NH2) was studied using its uniformly tritiated derivative. Experiments...     

LIG4 and RAD52 DNA repair genes polymorphisms and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with a strong genetic background. Nevertheless, SLE might also be triggered due to environmental factors, such as UV light exposure. DNA double strand breaks (DSBs) may be induced secondarily by UV radiation, increasing DNA immunogenicity and in SLE patients DNA repair is diminished, allowing the accumulation of DSBs and genomic instability. LIG4 and RAD52 genes play important roles in DNA repair mechanisms and a recent microarray analysis showed their differential expression in active SLE patients. In this study we investigated a potential association between LIG4 and RAD52 single nucleotide polymorphisms (SNPs) and SLE predisposition in a Southeast Brazilian population. We assessed four Tag SNPs in LIG4 and three in RAD52 gene region, encompassing most of the gene sequence, in 158 SLE patients and 212 healthy controls. We also performed SNPs analysis considering clinical manifestation, gender and ethnicity in SLE patients. Our data did not show association between LIG4 and RAD52 SNPs and SLE, its clinical manifestations or ethnicity in the tested population. The analysis regarding ethnicity and SLE clinical manifestations indicated Caucasian-derived patients as more susceptible to cutaneous and hematological alterations than the African-derived. To our knowledge, this is the first association study involving LIG4 and RAD52 genes and SLE predisposition.     

Renal Function in Hepatosplenic Schistosomiasis – An Assessment of Renal Tubular Disorders

Background

Renal involvement in Schistosoma mansoni infection is not well studied. The aim of this study is to investigate the occurrence of renal abnormalities in patients with hepatosplenic schistosomiasis (HSS), especially renal tubular disorders.

Methods

This is a cross-sectional study with 20 consecutive patients with HSS followed in a medical center in Maceió, Alagoas, Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl₂) after a 12-h period of water and food deprivation. The biomarker monocyte chemoattractant protein 1 (MCP-1) was quantified in urine. Fractional excretion of sodium (FE_Na+), transtubular potassium gradient (TTKG) and solute-free water reabsorption (TcH₂O) were calculated. The HSS group was compared to a group of 17 healthy volunteers.

Results

Patients'' mean age and gender were similar to controls. Urinary acidification deficit was found in 45% of HSS patients. Urinary osmolality was significantly lower in HSS patients (588±112 vs. 764±165 mOsm/kg, p = 0,001) after a 12-h period of water deprivation. TcH₂O was lower in HSS patients (0.72±0.5 vs. 1.1±0.3, p = 0.04). Urinary concentration deficit was found in 85% of HSS patients. The values of MCP-1 were higher in HSS group than in control group (122±134 vs. 40±28 pg/mg-Cr, p = 0.01) and positively correlated with the values of microalbuminuria and proteinuria.

Conclusions

HSS is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating ability and incomplete distal acidification defect, demonstrating the occurrence of tubular dysfunction. There was also an increase in urinary MCP-1, which appears to be a more sensitive marker of renal damage than urinary albumin excretion rate.     

Electrical activity in the vagus nerves and some medullary nuclei in rats: Changes induced by endotoxin action and hyperthermia evoked by an increase in ambient temperatures

Acute experiments on rats showed that intraperitoneal administration of 5 μg/kg of a bacterial toxin (pyrogenal) increases the afferent impulsation frequency in the cervical segments of vagus nerves, VN (multifiber recording), and frequency of the multineuronal activity in the solitary tract nucleus (STN); these changes were observed during the whole period of recording (10–160 min following toxin injection). Enhancement of the efferent impulsation in the VN and neuronal activity in the dorsal nucleus of the vagus nerve (DNVN) could be observed only 120–130 min after toxin administration. Under these conditions rectal temperature in experimental animals was 1.5° higher than that in control rats throughout the period of recording. Following subdiaphragmatic vagotomy, the afferent impulsation frequency in the cervical VN decreased about four times and kept on decreasing during the whole period of registration. Pyrogenal introduction evoked no changes in the direction of reactions to vagotomy. Under these conditions, body temperature of these animals was 2.5°C higher than in control vagotomized rats by the final stage of recording. Animal heating in a chamber caused no changes in the afferent impulsation frequency and resulted in a decrease in the frequency of VN efferent discharges. Involvement of the VN in the maintenance of temperature homeostasis during fever induced by the endotoxin action and by hyperthermia due to a rise in ambient temperature is discussed. Neirofiziologiya/Neurophysiology, Vol. 32, No. 2, pp. 112–119, March–April, 2000.     

The presence of macrophytes changes the beta diversity of Ephemeroptera,Plecoptera, and Trichoptera (EPT) assemblages in Cerrado streams in Northeastern Brazil

Limnology - In-stream conditions can affect the distribution of the Ephemeroptera, Plecoptera, and Trichoptera orders (EPT) because they require specific food resources and good quality water....     

Null allele in a human polymorphism restricted to the placenta: call for a search

The identification of a null allele in a human genetic system restricted to the placenta is a great challenge for two reasons: the impossibility of carrying out family studies and the unviability of sample recollections because the placenta itself is a disposable universe. Thus, in addition to reporting the finding of a null phenotype of placental alkaline phosphatase in a dark mulatto newborn from a black mixed population of Bahia, Brazil, here we present other evidence for the presence of the ALPP*Q0 allele with considerably high frequency in this population.     

Familial determinants of blood pressure in Northeastern Brazil

Summary Genetic heritability in this triracial population is 0.41 for systolic pressure in children, 0.14 for systolic pressure in adults, and 0.34 for diastolic pressure in both generations. Cultural inheritance is much smaller, and there is no evidence of maternal effects or major loci.