Association of TNF-308 G>A polymorphism located in tumor necrosis factor a with the risk of developing cervical cancer and results of pap smear

Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF-308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®-probes-based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval [CI]: 1.57-4.83, <0.001) and OR of 7.27 (95%CI: 2.5-20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF-308 G>A located on TNF-a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.     

Monophosphoryl Lipid A and Pam3Cys Prevent the Increase in Seizure Susceptibility and Epileptogenesis in Rats Undergoing Traumatic Brain Injury

Five percent of all epilepsy cases are attributed to traumatic brain injury (TBI), which are known as post-traumatic epilepsy (PTE). Finding preventive strategies for PTE is valuable. Remarkable feature of TBI is activation of microglia and subsequent neuroinflammation, which provokes epileptogenesis. The toll-like receptor agonists monophosphoryl lipid A (MPL) and tri-palmitoyl-S-glyceryl-cysteine (Pam3Cys) are safe, well-tolerated and effective adjuvants existing in prophylactic human vaccines. We examined the impact of early injection of MPL and Pam3Cys to rats, on the rate of kindled seizures acquisition following TBI. Rats received a single dose (1 µg/rat) of MPL or Pam3Cys through intracerebroventricular injection. 5 days later, trauma was exerted to temporo-parietal cortex of rats by controlled cortical impact device. After 24 h, traumatic rats underwent amygdala kindling. Brain level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was also measured in traumatic rats by immunoblotting. Compared to non-traumatic (sham-operated) rats, traumatic rats showed three times lower seizure threshold (133?±?5 µA vs. 416.3?±?16 µA, p?<?0.001); about three times less number of stimuli to become kindled (5?±?1 vs. 14?±?2, p?<?0.01); longer duration of kindled seizure parameters including entire seizure behavior, generalized seizures, and afterdischarges (p?<?0.001); and a two times increase in the TNF-α level. MPL and Pam3Cys did not change kindling rate and the seizure parameters in sham-operated rats. The MPL- and Pam3Cys-pretreated traumatic rats displayed seizure threshold, speed of kindling, and duration of kindled seizure parameters, similar to the non-traumatic rats. Pretreatment by MPL and Pam3Cys prevented the increase in TNF-α level by trauma. Given that MPL and Pam3Cys currently have clinical use as well-tolerated vaccines with reliable safety, they have the potential to be used in prevention of PTE.     

The effects of bicuculline and muscimol on glutamate-induced feeding behavior in broiler cockerels

This study was designed to examine the effects of intracerebroventricular (ICV) injection of bicuculline (GABA_A receptor antagonist) and muscimol (GABA_A receptor agonist) on glutamate-induced eating response in 24-h food-deprived (FD24) broiler cockerels. At first, guide cannula was surgically implanted in the right lateral ventricle of chickens. In experiment 1, birds were ICV injected with different doses of glutamate. In experiment 2, birds were administered with effective dose of glutamate after bicuculline. In experiment 3, chickens received muscimol prior to the injection of glutamate, and cumulative food intake was determined at 3-h postinjection. The results of this study showed that glutamate decreases food consumption in FD24 broiler cockerels (P ≤ 0.05), and this reduction occurs in a dose-dependent manner. Moreover, the inhibitory effect of glutamate on food intake was significantly increased with bicuculline pretreatment, and this effect was attenuated with muscimol (P ≤ 0.05). These results suggest that there is an interaction between glutamatergic and GABAergic systems (through GABA_A receptor) on food intake in broiler cockerels.     

Intracerebroventricular Injection of NMDA Receptor Antagonist Affects l-Arginine Induced Food Intake in Neonatal Layer Chicks

International Journal of Peptide Research and Therapeutics - Nowadays inquiry of possible interplay between different neurotransmitters in brain function is one of the major fields of interest for...     

Frequency of blaCTX-M and blaTEM Virulence Genes and Antibiotic Resistance Profiles among Klebsiella pneumoniae Isolates in Urinary Tract Infection (UTI) Samples from Hashtgerd,Iran

Background:Klebsiella pneumoniae (K. pneumoniae) is an opportunistic microorganism and one of the most important causes of urinary tract infection. This study aimed to evaluate the frequency of K. pneumoniae producing broad-spectrum beta-lactamase in urinary tract infection and to determine the pattern of drug resistance.Methods:This study was performed on 50 samples of K. pneumoniae isolated from patients with urinary tract infection referred to the Medical Diagnostic Laboratory in Hashtgerd city. The isolates were first evaluated for antibiotic susceptibility by disk diffusion method according to the method proposed by the Clinical and Laboratory Standards Institute (CLSI). Then phenotypic detection of ESBLS was carried out by the DDST method. The frequency of gene bla_TEM and bla_CTX-M was determined by PCR.Results:The highest resistance was observed to ampicillin (94%) and the highest sensitivity was observed to gentamicin (84%). 22 isolates (44%) were positive for ESBLs production. Of the 50 isolates studied, 34% had bla_CTX-M and 28% had bla_TEM and 11 (22%) had both genes simultaneously. Also, more than 77% of positive ESBLs isolates had the bla_CTX-M gene and approximately 63.64% of positive ESBLs isolates had the bla_TEM gene.Conclusion:Given the high prevalence of antibiotic-resistant and ESBL-producing isolates, early identification of these resistant isolates and their follow-up is essential to prevent further outbreaks. It is also important to use appropriate therapeutic strategies and proper and rational administration of antibiotics by physicians.Key Words: Antibiotic Resistance, ESBLs, K. pneumoniae, Urinary Tract Infection     

Interaction Between Central Opioidergic and Glutamatergic Systems on Food Intake in Neonatal Chicks: Role of NMDA,AMPA and mGLU1 Receptors

The present study was designed to examine the role of opioidergic and glutamatergic systems on feeding behavior in neonatal meat-type chicken. In experiment 1, FD₃ neonatal broilers ICV injected with (A) saline, (B) DAMGO (µ-opioid receptor agonist, 125 pmol), (C) MK-801 (NMDA glutamate receptors antagonist, 15 nmol) and (D) combination of DAMGO plus MK-801. Experiments 2–5 were similar to experiment 1, except FD₃ chicks ICV injected with CNQX (AMPA glutamate receptors antagonist, 390 nmol), AIDA (mGLU₁ receptors antagonist, 2 nmol), LY341495 (mGLU₂ receptors antagonist, 150 nmol) and UBP1112 (mGLU₃ receptors antagonist, 2 nmol) instead of MK-801, respectively. In experiments 6–10, FD₃ chicks ICV injected as the same as procedure to the experiments 1–5, except to inject with DPDPE (δ-opioid receptor agonist, 40 nmol) instead of the DAMGO. The experiments 11–15 were similar to the experiments 1–5, except neonatal broilers ICV injected with U-50488H (κ-opioid receptor agonist, 30 nmol) instead of DAMGO. Then the cumulative food intake measured until 120 min post injection. According to the results, ICV injection of DAMGO, significantly decreased food intake (P?<?0.05) while DPDPE and U-50488H increased feeding behavior compared to the control group (P?<?0.05). Co-injection of the DAMGO?+?MK-801 and DAMGO?+?AIDA, significantly decreased DAMGO-induced hypophagia in neonatal chicks (P?<?0.05). Also, co-injection of the DPDPE?+?CNQX significantly amplified DPDPE induced feeding behavior (P?<?0.05). These results suggested interconnection between central opioidergic and glutamatergic systems on feeding behavior mediates via µ- and δ-opioid receptor with NMDA, AMPA and mGLU₁ receptors in FD₃ neonatal broilers. These findings may shed light on the circuitry underlying interconnection between central opioidergic and glutamatergic systems on feeding behavior.