Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Synthesis, Raman, FT-IR, NMR spectroscopic characterization, antimicrobial activity, cytotoxicity and DNA binding of new mixed aza-oxo-thia macrocyclic compounds

Series of new mixed aza-oxo-thia macrocyclic ligands 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxo-5,13-dithia-cyclohexadecaphan-1⁴,9⁴-diphenyl (L₁); 1,10(2,6)-ditri azina-2,9,11,18-tetraaza-3,8,12,17-tetraoxo-5,6,14,15-tetrathia-cyclooctadecaphan-1⁴,10⁴-diphenyl (L₂); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetraoxo-6,16-dithia-cyclocosa-phan-1⁴,11⁴-diphenyl (L₃); 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraoxo-6,7,17,18-tetrathia-cyclodocosaphan-1⁴,12⁴-diphenyl (L₄) were synthesised. The structural features of the compounds have been studied by elemental analyses, Mass, FT-Raman, FT-IR, ¹H and ¹³C NMR spectroscopy. The antimicrobial activities of the ligands were evaluated using disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against several bacteria and yeast cultures. The obtained results from both methods were assessed in side-by-side comparison with commercial antibacterial and antifungal agents. In most cases, the compounds show strong antifungal activity in the comparison tests. Cytotoxic activities of the ligands against two different human cancer cell lines, stomach (23132/87) and lung (A549) were determined by MTT assay. DNA fragmentation assay tested cell lines were used to analyze the DNA ladder formation which is a characteristic of apoptotic cell death. The binding of the ligands with calf thymus DNA (CT-DNA) has also been investigated by absorption spectroscopy.     

Development and application of monoclonal antibodies for specific detection of human enteric adenoviruses.

Monoclonal antibodies were prepared against enteric adenovirus by fusing P3-NS1/-Ag4-1 mouse myeloma cells with lymphocytes from BALB/c mice immunized with enteric adenovirus 40 (Ad40) G2297. Of the several putative clones secreting antibodies to adenovirus, five were found to react specifically to the enteric adenovirus. The specificity of two of these monoclones which recognize a single antigen of a molecular size of 17 kilodaltons was evaluated against 78 clinical isolates. One monoclone (5D8/2C2) reacted with both Ad40 and Ad41, and the other monoclone (2H6/C11) recognized Ad40 only in an enzyme-linked immunosorbent assay (ELISA). These ELISA results correlated well with those of the specific neutralization test or DNA restriction endonuclease analysis or both. The use of this rapid ELISA with these monoclones will find applications in the diagnosis of enteric adenovirus and should facilitate the epidemiologic studies of enteric adenovirus gastroenteritis.     

Antibodies to human sperm YLP12 peptide that is involved in egg binding inhibit human sperm capacitation/acrosome reaction

Recently, the authors reported a novel dodecamer peptide sequence, designated as YLP12 on human sperm, that is involved in binding to zona pellucida (ZP) of human oocyte [10]. This unique sequence is present on the acrosomal region of the human sperm cell and is expressed only in human testis/ sperm. The aim of the present study was to examine whether YLP12 sequence is involved in capacitation/acrosome reaction. Swim-up sperm were capacitated with anti-YLP12 Fab' antibodies or control Fab's (40 and 85 microg/mL) and then the acrosome reaction was induced with calcium ionophore. An average of 64-73% sperm underwent acrosome reaction when they were capacitated in the presence of 40-85 microg/mL of bovine serum albumin or control Fab's. A significant (p < .01 to < .001) reduction (58-75%) in the percentage of acrosome-reacted sperm was observed when the sperm were capacitated in the presence of YLP12 Fab's. These data indicate that the YLP12 peptide sequence is involved in sperm capacitation / acrosome reaction, and may find clinical applications in the diagnosis and treatment of male infertility and immunocontraception.     

Prevalence and significance of MEFV gene mutations in patients with gouty arthritis

Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.     

Association of FcγRIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan

Dengue illness has been a major health concern in Pakistan during the last decade. Dengue infection can result in a spectrum of clinically distinct outcomes, ranging from asymptomatic infection to potentially life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A single-nucleotide polymorphism in FcγRIIa (rs1801274) results in altered affinity of the receptor for different subclasses of immunoglobulin G, and is a key player in determining the susceptibility to or protection from severe clinical infection of dengue. In this study, we analyzed the allelic and genotypic distribution of rs1801274 in subjects of Pakistani origin with subclinical dengue infection (n = 40), dengue fever (DF) (n = 40), and DHF/DSS (n = 30). We found that HH homozygotes and heterozygotes were significantly more likely to develop clinical dengue (odds ratio [OR] = 3.21, 95% confidence interval [CI] = 1.29–7.97, P = 0.009), either DF (OR = 2.82, 95% CI = 1.00–7.97, P = 0.045) or DHF/DSS (OR = 3.90, 95% CI = 1.13–13.07, P = 0.024) than the asymptomatic dengue infection. Results of allelic distribution comparisons and logistic regression analysis also supported the same relationship. The results suggest complex nature of interacting factors in determining the course for severe dengue illness.     

N‐acetyl cysteine attenuates diazinon exposure‐induced oxidative stress in rat testis

The aim of this study was to investigate the gonadotoxic effects of diazinon and its mechanism of action with special reference to its possible reactive oxygen species generating potential in rat testis and the protective effect of N‐Acetyl Cysteine (NAC) on the exposure of diazinon. The vehicle was given orally to the control group and NAC, diazinon, combination of NAC and diazinon were given to three treatment groups for 4 weeks. Testis lipid peroxidation levels were higher in diazinon group than in control although lipid peroxidation levels were lower in diazinon + NAC group than in diazinon group. The reduced glutathione (GSH) levels were lower in diazinon group than in control and NAC group although its levels were higher in diazinon + NAC group than in diazinon group. Vitamin C, Vitamin E and β‐carotene concentrations were also lower in diazinon group than in control and NAC groups. Vitamin E and β‐carotene concentrations were higher in diazinon + NAC group than diazinon group. Glutathione peroxidase activity and vitamin A concentrations in the testis did not show any difference between the four groups. In conclusion, we observed that NAC treatment modulated diazinon‐induced oxidative injury in the rat testis. These findings suggest that NAC supplementation can be useful in testis oxidative injury caused by the organophosphate insecticides.     

Unusual Case of West Nile Virus Flaccid Paralysis in a 10-Year-Old Child

West Nile virus infection is asymptomatic in most cases. West Nile virus neuroinvasive disease includes encephalitis, meningitis, and/or acute flaccid paralysis. In children, acute flaccid paralysis as the solo presentation of West Nile virus disease is rare. It develops abruptly and progresses rapidly early in the disease course. We report on a 10-year-old child who presented with a slowly progressive left leg flaccid paralysis over 4 weeks. He tested positive for West Nile virus in both blood and cerebrospinal fluid. Spinal MRI showed enhancement of the ventral nerve roots. This was also supported by electrophysiological studies. One week after the plateauing of his left leg paralysis, he was readmitted to the hospital with left hand weakness. Complete recovery of his recurrent weakness was observed after prompt 5-day course of intravenous immunoglobulin G therapy. However, no improvement was noticed in the left foot drop. To our knowledge, this is the first case report of West Nile virus disease in children presented with a slowly progressive flaccid paralysis, and a recurrent weakness recovered after intravenous immunoglobulin G administration.