Oxidative stress in small-for-gestational age (SGA) term newborns and their mothers

This study used malondialdehyde (MDA) determination by HPLC and enzymatic assays for total serum peroxides and antioxidant capacity to evaluate oxidative stress in 47 healthy full-term small-for-gestational age (SGA) newborns vs 67 appropriate-for-gestational age (AGA) newborns. Blood samples were collected at delivery from umbilical cord artery and vein and from peripheral blood of the babies on the third day after birth. Blood samples of mothers were also collected and compared with blood of 29 normal non-pregnant women (NPW). Serum peroxide values were significantly higher in both groups of mothers than in NPW, decreasing towards the third day in AGA mothers, while persisting in SGA mothers. Antioxidant capacity of sera of both groups of mothers was lower than NPW. Both SGA mothers and babies had increased MDA at delivery, unlike AGA counterparts. MDA levels in umbilical vein were higher than in umbilical arteries, while immunohistochemistry revealed abundant presence of 4-hydroxynonenal (HNE)-protein adducts only in stroma of the SGA placenta. These results show that both mothers and babies are exposed to oxidative stress during and after delivery, which is more pronounced and persistent in the perinatal period of the SGA group, while lipid peroxidation in placenta could play a role in SGA pathophysiology.     

Discovery of disubstituted piperidines and homopiperidines as potent dual NK1 receptor antagonists–serotonin reuptake transporter inhibitors for the treatment of depression

This report describes the synthesis, structure–activity relationships and activity of piperidine, homopiperidine, and azocane derivatives combining NK₁ receptor (NK₁R) antagonism and serotonin reuptake transporter (SERT) inhibition. Our studies culminated in the discovery of piperidine 2 and homopiperidine 8 as potent dual NK₁R antagonists-SERT inhibitors. Compound 2 demonstrated significant activity in the gerbil forced swimming test, suggesting that dual NK₁R antagonists-SERT inhibitors may be useful in treating depression disorders.     

Expression of matrix metalloproteinase-1 in uterosacral ligaments tissue of women with genital prolapse

Collagen metabolism is altered in the pelvic organ tissues of women with genital prolapse. The aim of this study was to compare collagen metabolism by measuring matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament tissues of postmenopausal women with and without genital prolapse. Uterosacral ligament tissues were obtained at the time of abdominal or vaginal surgery from twenty-four patients with pelvic organ prolapse (POP) and 21 women who underwent gynecologic surgery for benign indications. The tissue samples were analyzed by immunohistochemistry. There were no differences in age, BMI and parity between two groups. The patients with genital prolapse demonstrated significantly higher occurences of MMP-1 expression compared to controls. These findings indicate that increased MMP-1 expression in uterosacral ligaments is associated with genital prolapse. Our data are consistent with the theory that increased collagen breakdown may play an important role in the onset and development of pelvic organ prolapse (POP).     

Cross-talk between NKT and regulatory T cells (Tregs) in modulation of immune response in patients with colorectal cancer following different pain management techniques

Natural killer T (NKT) and regulatory T cells (Tregs) play an important role in innate immune response. Natural killer (NK) and NKT cells are indispensable factors in the body's ongoing defense against tumor development, as well as viral infection. NKT cells are a subset of T cells that shares properties of natural killer cells and conventional T cells. They are involved in innate immune responses, tumor rejection, post transplantation immunotherapy, immune surveillance and control of autoimmune diseases. They may also play both protective and harmful roles in the progression of certain autoimmune diseases, such as diabetes, lupus, atherosclerosis, and allergen-induced asthma. Immune surveillance involves the process whereby precancerous and malignant cells are recognized by the host immune system as damaged and are consequently targeted for elimination. The pharmacological management of postoperative pain in patients with malignancies uses very different techniques whose possible cytotoxic functions we still known very poor. The present study compared effects of two different postoperative pain management techniques in patients undergoing colorectal cancer surgery on the innate immunity. Our data indicate that the patients with colorectal cancer have significantly increased the percentage of Tregs and NKT cells. The values were statistically higher during epidural analgesia in comparison with intravenous analgesia, indicating that epidural pain management technique ameliorate the immune suppression after surgery.     

Epilepsy in the elderly and depression

Epilepsy is one of the most common neurological problems affecting approximately 1% of the world's population with higher incidence among elderly individuals. Although depression is a common comorbid condition in patients with epilepsy, there is a paucity of information regarding depression in geriatric patients with epilepsy. This study analysed a group of 83 patients affected by different epilepsy phenotypes accompanied by mental disorders, especially depression. Antiepileptic and antipsychotic drug treatment has been evaluated, particularly a positive effect of the new antiepileptics (monotherapy and polytherapy) both on the reduction of seizures and mental disorders.     

Distribution of hepatitis C virus genotypes in Croatia--a 10 year retrospective study of four geographic regions

The aim of this 10-year retrospective study was to investigate the distribution of HCV genotypes in patients with chronic hepatitis C monitored in the largest center for molecular diagnostics of HCV infection in Croatia. The study enrolled 1163 anti-HCV positive adults with detectable HCV RNA in the plasma. The patients were classified in four regions: Zagreb and surrounding continental area, Split, Slavonija and Rijeka. HCV genotyping was performed by using VERSANT HCV Genotyping Assay (LIPA) (Bayer Diagnostics, Puteaux Cedex, France). Statistical analysis was performed by using Statistica for Windows V.5.1. The majority of HCV infections in the study population were caused by genotypes 1 (58.8% of infected patients) and 3 (35.6%). Percentages of patients infected with subtypes 1b and 1a were 37.4% and 13.1%, respectively. Genotypes 2 and 4 were present in a very low percentage of patients (2.2% and 3.4%, respectively) while genotypes 5 and 6 were not detected. Analysis of regional differences in the distribution of HCV genotypes revealed similar percentages of subtype 3a and 1b infections in the Split region while the majority of infections in other regions were caused by subtype 1b. Infections with genotypes 2 and 4 were present in less than 5% of patients in all geographic regions. Analysis of an association between risk factors for infection and distribution of genotypes and subtypes in a subset of patients from the Split region confirmed the association between IVDU and subtype 3a. We conclude that the prevalence of HCV genotypes and subtypes follows the pattern of other Southern and Eastern European Countries with the predominance of subtypes 1b, 3a and 1a.     

Changes in T-cell subpopulations during four years of suppression of HIV-1 replication in patients with advanced disease

We compared the number/percentages of naive and memory CD4+ T-cells, CD38+ CD8+ T-cells, and CD28+ CD4+ and CD28+ CD8+ T-cells in patients with advanced HIV disease (baseline CD4+ count < 100) with those with less advanced (baseline CD4+ cell count > 100) HIV disease during 4 years of suppressive highly active antiretroviral therapy. This prospective, longitudinal study included 30 treatment-naive patients and 32 controls. Advanced HIV-infected patients (n = 13) gained more CD4+ T-cells than less advanced patients (n = 11) at 1 month (median: 60 vs. 36 microL(-1)), 3 months (86 vs. 14), 6 months (111 vs. 23), 12 months (174 vs. 47), 24 months (162 vs. 72) and 48 months (257 vs. 123) (P = 0.15, P < 0.001, P = 0.026, P = 0.021, P = 0.1 and P = 0.06, respectively). Advanced patients gained more naive CD4+ T-cells at 48 months compared to less advanced patients (27.3 vs. 11.4%, P = 0.05). The relative gain in memory CD4+ T-cells was greater in advanced vs. less advanced patients at 1 month (median: 6.4 vs. 1.4%), 3 months (4.3 vs. 2.0), 6 months (6.7 vs. 1.6), 12 months (6.9 vs. 2.4), 24 months (7.5 vs. 3.1) and 48 months (11.3 vs. 6.8) (P = 0.002, P = 0.013, P < 0.001, P = 0.004, P = 0.001 and P = 0.015, respectively). At 48 months, CD38+ CD8+ T-cells and naive CD4+ T-cells reached normal values (9.2%, P = 0.869 vs. controls and 47.5%, P = 0.699, respectively) in less advanced patients, as did CD38+ CD8+ T-cells in advanced patients (4.7%, P = 0.309 vs. controls). The kinetics of naive and memory CD4+ T-cell reconstitution is different in less advanced compared to advanced HIV patients.     

Formulations for delivery of therapeutic proteins

Advances in biotechnology have now created a capacity to produce therapeutically active proteins on a commercial scale, opening the potential for their application in an array of disease conditions. The process of translation of the variety of different therapeutic proteins into the medicines used in clinics is now occurring. To assist in this translation, new formulations to deliver proteins could play an important role. These new formulations need to more adequately address the pharmacological and therapeutic requirement for each particular protein/peptide and, in that way, either improve present therapies or extend with new entries the current list of protein based medicines used in clinic.