EVALUATION OF CHEMOPREVENTIVE RESPONSE OF PENTOXIPHYLLINE AND SILDENAFIL IN COLORECTAL CARCINOMA EXPERIMENTALLY INDUCEDIN RATS: COMPARATIVE STUDY WITH 5-FLUOROURACIL

Objective: This study was designed to investigate some possible therapeutic mechanisms of pentoxifylline and sildenafil in the treatment of colorectal carcinoma induced by 1, 2 dimethylhydrazines in rats.Methods: Rats were allocated into seven groups, negative control, colon cancer induced by 1,2,dimethylhydrazine, 5-fluorouracil (5-FU) (50 mg/kg)-treated, pentoxifylline (PTX) (50 mg/kg)-treated, sildenafil (0.7 mg/kg)-treated groups; the two other groups set as colon cancer induced group treated with PTX (50 mg/kg) plus 5-FU(50 mg/kg) and sildenafil (0.7 mg/kg) plus 5-FU (50 mg/kg), respectively.Results: Biochemical results revealed significant elevation of serum carcinoembryonic antigen (CEA) levels, carbohydrate19-9 antigen (CA19-9) as colon cancer specific antigen markers; and a significant decrease in scaspase-3 (CASP3) as a marker for apoptosis, in the cancer-induced group compared to negative control group. Cancer-induced rats treated with 5-FU, with PTX or sildenafil showed a significant decrease in serum CEA and CA19-9 levels and a significant increase in CASP3 levels compared to cancer induced group. Furthermore, plasma levels of CEA and CA19-9 in 5-FU plus pentoxifylline and in 5-FUplus sildenafil groups were significantly decreased and plasma levels of CASP3 in 5-FU plus PTX, 5-FU plus sildenafil groups were significantly increased with respect to 5-FU treated group.Conclusion: Results of the present study suggest a good therapeutic approach of the PDE inhibitors, PTX and sildenafil for intervention against progressive colon cancer with special reference to the induction of apoptosis in colon cancer cells.Â

The Health-Related Quality of Life, Work Productivity, Healthcare Resource Utilization, and Economic Burden Associated with Levels of Suicidal Ideation Among Patients Self-Reporting Moderately Severe or Severe Major Depressive Disorder in a National Survey.

Background: Suicidal ideation (SI) is a cardinal aspect of major depressive disorder (MDD); however, patient-reported outcomes data from large-scale surveys are limited concerning SI in the context of MDD. This study aims to understand the association between varying levels of SI and health-related quality of life (HRQoL), work productivity, healthcare resource utilization (HRU), and associated costs in patients with moderately severe/severe MDD. Methods: This was a retrospective, cross-sectional analysis of 2013 national survey data. Patients who self-reported moderately severe or severe MDD and completed the Short Form Survey Version 2 (SF-36v2), Work Productivity Loss and Activity Impairment questionnaire (WPAI), and questions related to HRU were analyzed. Direct and indirect costs were calculated. Patients were categorized and analyzed by the level of SI (no SI, low, moderate, and high) based on their response to Item 9 of the Patient Health Questionnaire-9. Results: Among 75,000 respondents, 15.3% self-reported receiving a physician diagnosis of moderately severe or severe MDD and 2.8% of the total sample endorsed some level of SI. Patients with high SI showed a higher burden than patients with no SI, reporting lower mean SF-36v2 mental component summary scores ( Conclusion: Higher levels of SI were associated with lower HRQoL, greater HRU, and more work impairment resulting in higher direct and indirect costs compared with patients with MDD but no SI. These results highlight the need to implement effective treatment models and interventions in the employed population

The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons

During the course of normal aging, certain populations of nerve growth factor (NGF)-responsive neurons become selectively vulnerable to cell death. Studies using dissociated neurons isolated from neonates have shown that c-Jun N-terminal kinases (JNKs) are important in regulating the survival and neurite outgrowth of NGF-responsive sympathetic neurons. Unlike neonatal neurons, adult sympathetic neurons are not dependent on NGF for their survival. Moreover, the NGF precursor, proNGF, is neurotoxic for aging but not young adult NGF-responsive neurons. Because of these age-related differences, the effects of JNK inhibition on the survival and growth of sympathetic neurons isolated from aged mice were studied. Aged neurons, as well as glia, were found to be dependent on JNK for their growth but not their survival. Conversely, proNGF neurotoxicity was JNK-dependent and mediated by the p75-interacting protein NRAGE, whereas neurite outgrowth was independent of NRAGE. These results have implications for the potential use of JNK inhibitors as therapies for ameliorating age-related neurodegenerative disease

Impact of Al-Najebiya thermal energy power plant on aquatic ecosystem of Garmat Ali canal.

Monthly variations in concentrations of nutrients (nitrite, nitrate, phosphate and silicates) along with total dissolved solids (TDS) were investigated in Al-Najebiya electricity power generating station (N.S).The study extended from November 1997 to October 1998. Three sites were selected for sampling, based on intake and discharge points. The lowest nitrite value (0.15 µg at. N/L) was encountered in November and the highest (1.37 µg at. N/L) in January. Nitrate (NO3) revealed considerable rise in concentrations near effluent, as well, and the highest (34.95 µg at. N/L) was in August. Maximum value of phosphate (4.75 µg at. P/L) was encountered near the effluent discharging point. Silicate (SiO3) concentration was also distinctly high in this site, the maximum value (201.1 µg at. Si/L) recorded in August. TDS exhibited higher concentrations in sites closer to thermal discharge as well (1675mg/L). No previous ecological, long or short term, work of the type was recorded for the investigated site or any other similar locations in the country.

Impact of Al-Najebiya thermal energy power plant on aquatic ecosystem of Garmat Ali canal.

Monthly variations in concentrations of nutrients (nitrite, nitrate, phosphate and silicates) along with total dissolved solids (TDS) were investigated in Al-Najebiya electricity power generating station (N.S).The study extended from November 1997 to October 1998. Three sites were selected for sampling, based on intake and discharge points. The lowest nitrite value (0.1

Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice.

Alpha-synuclein (α-Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that α-Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing α-Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used α-Syn small interfering RNA (siRNA) to reduce total and aggregated α-Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease α-Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation-mimic S129D α-Syn, which exhibits aggregation. In normal mice we detected significantly reduced α-Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG-exosomes loaded with siRNA to α-Syn. In S129D α-Syn transgenic mice we found a decreased α-Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG-exosome delivery of siRNA to delay and reverse brain α-Syn pathological conditions

Self-medication among medical students in Anbar and Fallujah Universities – Iraq

Background: Self-medication (SM) is a worldwide issue, that has serious adverse effects on individuals and communities. Objective:  To estimate the prevalence of self- medication   among medical student in Anbar and Falluja Universities and to explore the important reasons for using self-medication.  To identify the common sources and types of self-medication drugs. Method: A descriptive cross-sectional study was carried out among medical students in Anbar   and Fallujah Universities during the period from February to March 2018.  The subjects were asked to fill a questionnaire that consisted of questions on age, gender and educational level, in addition to questions for self-medication history. Results: The results revealed that 73% of medical students had practice of self- medication. A higher prevalence of self-medication was  found among 5th study year students. Antibiotics were the most frequent self-prescribe medicine that used by 137 (49.6%) of the participants, followed by analgesic (29%), and supplements by 40 (14.5%).  The most frequently given reasons for using self-medication were previous prescription and of pharmacists’ advice. Conclusion: A high prevalence of self- medication was found among medical students in Falluja & Anbar Universities with a statistical significant association between gender and self- medication practice

The Q loops of the human multidrug resistance transporter ABCB1 are necessary to couple drug binding to the ATP catalytic cycle

For a primary active pump, such as the human ATP-binding-cassette (ABC) transporter ABCB1, coupling of drug-binding by the two transmembrane domains (TMDs) to the ATP catalytic cycle of the two nucleotide-binding domains (NBDs) is fundamental to the transport mechanism, but is poorly understood at the biochemical level. Structure data suggest that signals are transduced through intracellular loops of the TMDs that slot into grooves on the NBDs. At the base of these grooves is the Q loop. We therefore mutated the eponymous glutamine in one or both NBD Q loops and measured the effect on conformation and function by using a conformation-sensitive antibody (UIC2) and a fluorescent drug (Bodipy-verapamil), respectively. We showed that the double mutant is trapped in the inward-open state, which binds the drug, but cannot couple to the ATPase cycle. Our data also describe marked redundancy within the transport mechanism, because single-Q-loop mutants are functional for Bodipy-verapamil transport. This result allowed us to elucidate transduction pathways from twin drug-binding cavities to the Q loops using point mutations to favor one cavity over the other. Together, the data show that the Q loop is the central flexion point where the aspect of the drug-binding cavities is coupled to the ATP catalytic cycle.-Zolnerciks, J. K., Akkaya, B. G., Snippe, M., Chiba, P., Seelig, A., Linton, K. J. The Q loops of the human multidrug resistance transporter ABCB1 are necessary to couple drug binding to the ATP catalytic cycle