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Anti-cancer Prodrugs-Three Decades of Design
(2015-07-31) Horani, Waad; Thawabteh, Ameen; Scrano, Laura; A. Bufo, Sabino; Mecca, Gennaro; Karaman, Rafik
The conventional old treatment method for cancer therapy is associated with severe side effects along with several limitations. Therefore, searching and developing new methods for cancer became crucial. This mini review was devoted on the design and synthesis of prodrugs for cancer treatment. The methods discussed include targeted prodrugs which are depending on the presence of unique cellular conditions at the desired target, especially the availability of certain enzymes and transporters at these target sites, antibody directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) which is considered one of the important strategies for the treatment of cancer and prodrugs based on enzyme models that have been advocated to understand enzyme catalysis. In this approach, a design of prodrugs is accomplished using computational calculations based on molecular orbital and molecular mechanics methods. Correlations between experimental and calculated rate values for some intramolecular processes provided a tool to predict thermodynamic and kinetic parameters for intramolecular processes that can be utilized as prodrugs linkers. This approach does not require any enzyme to catalyze the prodrug interconversion. The interconversion rate is solely dependent on the factors govern the limiting step of the intramolecular process.
Antibacterial Predrugs-from 1899 till 2015
(WJPPS,Dr. T Pal, 2015-07-08) Elayyan, Sabrin; Karaman, Donia; Mecca, Gennaro; Scrano, Laura; Bufo, Sabino A.; Karaman, Rafik
The predrug (prodrug) term involves chemically modified inert compound which upon an administration releases the active parent drug to elicit its pharmacological response within the body. For many years, the predrug strategy has been extensively developed to solve many unwanted drug properties. This approach has several advantages over conventional drug administration and it has the potential to be quite effective method for the treatment of diseases in the future. In this mini-review we describe a number of antibacterial agents‘ predrugs, and the ways by which predrug strategy was exploited to overcome many pharmaceutical and pharmacokinetic problems that the parent active antibacterial drugs suffer from such as, low bioavailability by increasing or decreasing lipophilicity, site selectivity for higher absorption and less toxicity, short duration of action to increase patient compliance, rapid metabolism to increase oral bioavailability and masking bitter sensation which is crucial for geriatric and pediatric patient compliance.
Assessment of Patient Safety Culture in the Palestinian Hospital Pharmacies
(AL-Quds University, 2011) وفاء جمال حسن الزغاري; Wafa Jamal Hassan Zaghari; معتصم حمدان; Hussein Hallak; Ali Shaar
Background: Patient safety culture assessment in pharmacies is increasing largely worldwide, many tools that were used to assess patient safety culture at the hospital settings as a whole are now adapted to be used for pharmacies. One of the most commonly used and rigorously validated tools to measure patient safety culture is the Safety Attitudes Questionnaire (SAQ). The tool consists of 30 items that cover six safety culture domains. The intention of this research is to map the patient safety culture in the Palestinian hospital pharmacies, this will be achieved through measuring and analyzing the patient safety culture domains there, understanding factors influencing safety culture and examine variations between different hospital pharmacies. This assessment helps in determining safety culture domains that are considered as areas of strength, and safety culture domains that are considered as areas of weakness for each hospital pharmacy. Mapping patient safety culture in hospital pharmacies will end up by directing each hospital pharmacy to improve areas of weakness effectively and efficiently. Purpose: To assess patient safety culture in the Palestinian hospital pharmacies, and to assess the association of hospitals and respondents characteristics with patient safety culture. Methods: A cross-sectional design was used. The English version of the SAQ was translated and adapted to the Palestinian context. The survey was carried out in (28) Palestinian hospitals in the West Bank and East Jerusalem. All pharmacist assistants, pharmacist, and clinical pharmacists in these hospitals were targeted, estimated to 115 personnel. Items mean and scale scores were calculated. Then a composite score equivalent to the arithmetic mean of the scale scores were also calculated. In order to identify areas of strength and areas for potential improvement, the percentages of positive responses for the survey domains and items were calculated. Univariate analysis was used to test associations between composite patient safety scores and different respondent and hospital characteristics. viii Findings: 73 persons participated in the study, response rate was 68.8%. Females were 66.7%, 51% were pharmacist or clinical pharmacist, and 84.7% were with experience ≥ 5 years in profession. Two SAQ domains, job satisfaction and working conditions, were identified as areas of strength and received ≥75% of positive responses. Patient safety level was graded as “accepted” by (50%) of the respondents and none gave their pharmacy a “Poor” or “Failing” grade. Event reporting was very low, (66%) of the respondents didn’t report any event in the past year. In regard to the associations between safety culture domains scores with participants and hospital characteristics, the association was statistically significant (P<0.05) in regard to hospital ownership with the teamwork climate (P=0.02), perception of management (P=0.03), job satisfaction (P=0.001), and working conditions (P=0.02) and all in favor of the private and NGO hospitals. Participants working in hospitals sized <50 beds were more positive towards perception of management climate than their counterparts in larger sized hospitals (P=0.031). The overall safety score was significantly associated only with the hospital ownership (P=0.002) in favor of the private and NGO hospitals. No statistically significant associations were found between safety culture domains and the participant’s age, gender, years of experience in profession and hospital, level of education, working hours, and job title. The safety culture domain scores varied largely among different hospital pharmacies. None of the six domains were positive for four hospitals, twelve hospitals have negative total safety score and the best result was having five positive safety domains and a positive total safety score and this result was achieved only by two hospitals. Conclusions: Safety culture assessment results revealed areas for potential improvement in Palestinian hospital pharmacies. Hospitals need to formulate specific patient safety culture interventions to address these weaknesses
Binding of Vitamin K1(Phylloquinone) to Human Serum Albumin(HSA):Spectroscopic studies
(Dr.V.K.Sharma, 2014-09-07) Abu Teir, Musa M; Hourani, Ola; Darwish, Saker M; Abu-hadid, Mahmoud M
The interaction of hydrophobic vitamin (vitamin K1) with human serum albumin (HSA) at physiological (pH 6.9- 7.4) has been studied using UV-VIS spectrometer, and an FT-IR spectroscopy. The interaction of hydrophobic vitamin (vitamin K1) with HSA has been investigated by using UV-absorption, and Fourier transforms infrared (FT-IR) spectroscopy. The binding constant of vitamin K1 has been determined by UV-absorption. The value of the binding constant for vitamin K1 -HSA is calculated at room temperature 293 K and it was determined as 60 M��. FT-IR spectroscopy with Fourier self- deconvolution technique and second derivative resolution enhancement procedures were applied in the analysis of the amide I, amid II, and amid III regions to determine the protein secondary structure and hydrophobic vitamin binding mechanisms. All peaks positions in the three amide regions (amid I, amide II and amide III) have been assigned and any changes due to concentration changes have been investigated. The FTIR spectra measurements indicate a change in the intensity of absorption bands due to change in the concentrations in drugs. In addition a larger intensity decrease in the absorption band of α-helix relative to that of β-sheets has been observed. This variation in intensity is related indirectly to the formation of H-bonding in the complex molecules, which accounts for the different intrinsic propensities of α-helix and β-sheets.
Biophysical Interaction of Propylthiouracil with Human and Bovine Serum Albumins
(BMC, 2019-01-30) Alsamamra, Husain; Abuteir, Musa; Darwish, Saqer
The physical interaction of antithyroid drug, propylthiouracil was studied with bovine and human serum albumins through UV absorption and fluorescence spectroscopic techniques. The obtained values of the quenching constants were calculated by the Stern-Volmer equation are in the order of 1012 Lmol-1 s-1 indicating that both serum albumins were quenched by the drug in a static manner. The binding constants of the drug interaction with both HSA and BSA proteins are found to be relatively weak and are in the order of 103 M-1. The tryptophan residues of HSA and BSA are most perturbed by the binding process which was authenticated by the fluorescence spectra of both proteins in the presence of propylthiouracil. The importance behind this study is to clarify the mechanism of the interaction between propylthiouracil with HSA and BSA, as well as providing additional values in order to study drug-protein interaction which may facilitate the study of drug metabolism and transportation.
Computationally Designed Enzyme Models to Replace Natural Enzymes in Prodrug Approaches
(2012-11-16) Karaman, Rafik
The striking efficiency of enzyme catalysis has inspired many organic chemists to explore enzyme mechanisms by studying certain intra molecular processes such as enzyme models which proceed faster than their intermolecular counterparts. This research brings about the important question of whether enzyme models will replace natural enzymes in the conversion of prodrugs to their parental drugs. Enzymes are mandatory for the inter conversion of many prodrugs to their parental drugs. Among the most important enzymes in the bioconversion of prodrugs are amides (ex. trypsin, chymotrypsin, elastase, carboxypeptidase, and aminopeptidase) and ester-based prodrugs (ex. paraoxonase, carboxylesterase, acetylcholinesterase and cholinesterase). Most of these enzymes are hydrolytic enzymes, however, non-hydrolytic enzymes, including all cytochrome P450 enzymes, are also capable of catalyzing the bioconversion of ester and amide-based prodrugs [1].
Cost-utility analysis of a pharmacy-led self-management programme for patients with COPD
(Springer Science+Business Media B.V. 2011, 2011-06-04) Khdour, Maher R.; Agus, Ashley M.; Kidney, Joseph C.; Smyth, Bronagh M.; Elnay, James C.; Crealey, Grainne E.
Objective: To undertake a cost-utility analysis (CUA) of a pharmacy-led self-management programme for Chronic Obstructive Pulmonary Disease (COPD). Setting: A single outpatient COPD clinic at the Mater Hospital, Belfast, Northern Ireland between. Method: CUA alongside a randomised control trial. The economic analysis used data from 127 COPD patients aged over 45 years, with an FEV1 of 30–80% of the predicted normal value. Participants received either a pharmacy-led education and selfmanagement programme, or usual care. One year costs were estimated from the perspective of the National Health Service and Personal Social Services and quality-adjusted life years (QALYs) were calculated based on responses to the EQ-5D at baseline, 6 and 12 months. Main outcome measure: Cost per QALY gained. Results: The mean differences in costs and effects between the self-management and education programme and usual care were -£671.59 (95 CI%: -£1,584.73 to -£68.14) and 0.065 (95% CI; 0.000–0.128). Thus the intervention was the dominant strategy as it was both less costly and more effective than usual care. The probability of the intervention being costeffective was 95% at a threshold of £20,000/QALY gained. Sensitivity analyses indicated that conclusions were robust to variations in most of the key parameters. Conclusion: The self-management and education programme was found to be highly cost-effective compared to usual care. Further research is required to establish what aspects of self-management and education programmes have the greatest impact on cost-effectiveness.
Depression Impairs Learning, whereas the Selective Serotonin Reuptake Inhibitor, Paroxetine, Impairs Generalization in Patients with Major Depressive Disorder
(Elsevier, 2014-11-01) Herzallah, Mohammad M.; Moustafa, Ahmed A.; Natsheh, Joman Y.; Danoun, Omar A.; Simon, Jessica R.; Tayem, Yasin I.; Sehwail, Mahmud A.; Amleh, Ivona; Bannoura, Issam; Petrides, Georgios; Myers, Catherine E.; Gluck, Mark A.
To better understand how medication status and task demands affect cognition in Major Depressive Disorder (MDD), we evaluated medication-naïve patients with MDD, medicated patients with MDD receiving the Selective Serotonin Reuptake Inhibitors (SSRI) paroxetine, and healthy controls. All three groups were administered a computer-based cognitive task with two phases, an initial phase in which a sequence is learned through reward-based feedback (which our prior studies suggest is striatal-dependent), followed by a generalization phase that involves a change in the context where learned rules are to be applied (which our prior studies suggest is hippocampal-region dependent). Medication-naïve MDD patients were slow to learn the initial sequence but were normal on subsequent generalization of that learning. In contrast, medicated patients learned the initial sequence normally, but were impaired at the generalization phase. We argue that these data suggest (i) an MDD-related impairment in striatal-dependent sequence learning which can be remediated by SSRIs and (ii) an SSRI-induced impairment in hippocampaldependent generalization of past learning to novel contexts, not otherwise seen in the medicationnaïve MDD group. Thus, SSRIs might have a beneficial effect on striatal function required for sequence learning, but a detrimental effect on the hippocampus and other medial temporal lobe structures critical for generalization.
Diabetes mellitus: The epidemic of the century
(Baishideng Publishing Group Inc., 2015-06-25) Kharroubi, Akram T; Darwish, Hisham M
The epidemic nature of diabetes mellitus in different regions is reviewed. The Middle East and North Africa region has the highest prevalence of diabetes in adults (10.9%) whereas, the Western Pacific region has the highest number of adults diagnosed with diabetes and has countries with the highest prevalence of diabetes (37.5%). Different classes of diabetes mellitus, type 1, type 2, gestational diabetes and other types of diabetes mellitus are compared in terms of diagnostic criteria, etiology and genetics. The molecular genetics of diabetes received extensive attention in recent years by many prominent investigators and research groups in the biomedical field. A large array of mutations and single nucleotide polymorphisms in genes that play a role in the various steps and pathways involved in glucose metabolism and the development, control and function of pancreatic cells at various levels are reviewed. The major advances in the molecular understanding of diabetes in relation to the different types of diabetes in comparison to the previous understanding in this field are briefly reviewed here. Despite the accumulation of extensive data at the molecular and cellular levels, the mechanism of diabetes development and complications are still not fully understood. Definitely, more extensive research is needed in this field that will eventually reflect on the ultimate objective to improve diagnoses, therapy and minimize the chance of chronic complications development.
Diabetes mellitus: The epidemic of the century
(Baishideng Publishing Group Inc., 2015-06-25) Kharroubi, Akram T; Darwish, Hisham M
The epidemic nature of diabetes mellitus in different regions is reviewed. The Middle East and North Africa region has the highest prevalence of diabetes in adults (10.9%) whereas, the Western Pacific region has the highest number of adults diagnosed with diabetes and has countries with the highest prevalence of diabetes (37.5%). Different classes of diabetes mellitus, type 1, type 2, gestational diabetes and other types of diabetes mellitus are compared in terms of diagnostic criteria, etiology and genetics. The molecular genetics of diabetes received extensive attention in recent years by many prominent investigators and research groups in the biomedical field. A large array of mutations and single nucleotide polymorphisms in genes that play a role in the various steps and pathways involved in glucose metabolism and the development, control and function of pancreatic cells at various levels are reviewed. The major advances in the molecular understanding of diabetes in relation to the different types of diabetes in comparison to the previous understanding in this field are briefly reviewed here. Despite the accumulation of extensive data at the molecular and cellular levels, the mechanism of diabetes development and complications are still not fully understood. Definitely, more extensive research is needed in this field that will eventually reflect on the ultimate objective to improve diagnoses, therapy and minimize the chance of chronic complications development.
Diclofenac Codrugs and Prodrugs-Three Decades of Design
(‎WJPPS,Dr. T Pal, 2015-06-08) Dweib, khuloud; Jumaa, Salma; Thawabteh, Ameen; Scrano, Laura; Bufo, Sabino A.; Mecca, Gennaro; Karaman, Rafik
Prodrugs or predrugs are inactive molecules which become active after in vivo conversion to release the active parent drug. The prodrug’s cleavage can be catalyzed by metabolic enzymes or can occur by chemical means without the involvement of enzymes. Prodrugs are designed to improve undesirable physicochemical and pharmacokinetic properties of their parent drugs. Non-steroidal anti-inflammatory (NSAIDs) drugs are among the most commonly used drugs for treatment of pain, inflammation and fever. Despite their frequent use, these agents suffer from gastrointestinal side effects that limit their use for those patients with gastrointestinal conditions. This mini review discusses the design, synthesis and pharmacological effects of prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs) Diclofenac sodium or potassium. It argues that the prodrug approach has the potential to eliminate Diclofenac associated gastrointestinal complications, increases its bioavailability and masks its bitter taste.
Dissociating the Cognitive Effects of Levodopa versus Dopamine Agonists in aNeurocomputational Model of Learning in Parkinson's Disease
(Karger AG, Basel, 2012-11-01) Moustafa, Ahmed A.; Herzallah, Mohammad M.; Gluck, Mark A.
Background/Aims: Levodopa and dopamine agonists have different effects on the motor, cognitive, and psychiatric aspects of Parkinson’s disease (PD). Methods: Using a computational model of basal ganglia (BG) and prefrontal cortex (PFC) dopamine, we provide a theoretical synthesis of the dissociable effects of these dopaminergic medications on brain and cognition. Our model incorporates the findings that levodopa is converted by dopamine cells into dopamine, and thus activates prefrontal and striatal D 1 and D 2 dopamine receptors, whereas antiparkinsonian dopamine agonists directly stimulate D 2 receptors in the BG and PFC (although some have weak affinity to D 1 receptors). Results: In agreement with prior neuropsychological studies, our model explains how levodopa enhances, but dopamine agonists impair or have no effect on, stimulus-response learning and working memory. Conclusion: Our model explains how levodopa and dopamine agonists have differential effects on motor and cognitive processes in PD.
Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331 288 participants.
(2015-06-22) Abdeen, Ziad
Background Diabetes has been defi ned on the basis of diff erent biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA1c. We assessed the eff ect of diff erent diagnostic defi nitions on both the population prevalence of diabetes and the classifi cation of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in diff erent regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defi ning diabetes. Diabetes was defi ned using HbA1c (HbA1c ≥6·5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT defi nitions (FPG ≥7·0 mmol/L or 2hOGTT ≥11·1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using diff erent defi nitions graphically and by regression analyses. We calculated sensitivity and specifi city of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specifi city in each survey, and then pooled results using a random-eff ects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG-or-2hOGTT was correlated with prevalence based on FPG alone (r=0·98), but was higher by 2–6 percentage points at diff erent prevalence levels. Prevalence based on HbA1c was lower than prevalence based on FPG in 42·8% of age–sex–survey groups and higher in another 41·6%; in the other 15·6%, the two defi nitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA1c-based prevalences was partly related to participants’ age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specifi c communities. Diabetes defi ned as HbA1c 6·5% or more had a pooled sensitivity of 52·8% (95% CI 51·3–54·3%) and a pooled specifi city of 99·74% (99·71–99·78%) compared with FPG 7·0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defi ned based on FPGor- 2hOGTT was 30·5% (28·7–32·3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA1c versus FPG.
Evaluation of Glycated Hemoglobin (HbA1c) for Diagnosing Type 2 Diabetes and Prediabetes among Palestinian Arab Population
(Public Library of Science, 2014-02-04) Kharroubi, Akram T.; Darwish, Hisham M.; Abu Al-Halaweh, Ahmad I.; Khammash, Umaiyeh M.
The purpose of the study is to compare the potential of HbA1c to diagnose diabetes among Palestinian Arabs compared to fasting plasma glucose (FPG). A cross-sectional sample of 1370 Palestinian men (468) and women (902) without known diabetes and above the age of 30 years were recruited. Whole blood was used to estimate HbA1c and plasma for FPG and total lipid profile. Fasting plasma glucose was used as a reference to diagnose diabetes ($ 126 mg/dL) and prediabetes (100–125 mg/dL). The area under the receiver operating characteristic curve (AUC) for HbA1c was 81.9% to diagnose diabetes and 63.9% for prediabetes. The agreement between HbA1c and diabetes as diagnosed by FPG was moderate (K = 0.498) and low with prediabetes (K = 0.142). The optimal cut-off value for HbA1c to diagnose diabetes was $ 6.3% (45 mmol/mol). The sensitivity, specificity and the discriminant ability were 65.6% (53.1–76.3%), 94.5% (93.1–95.6%), 80.0% (72.8–87.3%), respectively. However, using cut-off value of $ 6.5% (48 mmol/mol) improved specificity. At this cut-off value, the sensitivity, specificity and the discriminant ability were 57.4% (44.9–69.0%), 97.1% (96.0–97.9%) and 77.3% (71.0–83.5%). For diagnosing prediabetes with HbA1c between 5.7–6.4% (39–46 mmol/mol), the sensitivity, specificity and the discriminant ability were 62.7% (57.1–67.9%), 56.3% (53.1–59.4%) and 59.5% (56.3–62.5%), respectively. HbA1c at cut-off value of $ 6.5% (48 mmol/mol) by itself diagnosed 5.3% and 48.3% as having diabetes and prediabetes compared to 4.5% and 24.2% using FPG, respectively. Mean HbA1c and FPG increase significantly with increasing body mass index. In conclusion, the ROC curves showed HbA1c could be used for diagnosing diabetes when compared to FPG but not for prediabetes in Palestinians Arabs even though only about 50% of the diabetic subjects were identified by the both HbA1c and FPG.
Extent and nature of unlicensed and off-label medicine use in hospitalized children in Palestine
(Springer, 2011-05-13) Hussein Hallak; Maher khdour; Alayasa, Kawther; AlShahed, Qusai; Hawwa, Ahmed; McElnay, James
Objective of the study To determine the extent and nature of unlicensed/off-label prescribing patterns in hospitalised children in Palestine. Setting Four paediatric wards in two public health system hospitals in Palestine [Caritas children’s hospital (Medical and neonatal intensive care units) and Rafidia general hospital (Medical and surgical units)]. Method A prospective survey of drugs administered to infants and children \18 years old was carried out over a five-week period in the four paediatric wards. Main outcome measure Drug-licensing status of all prescriptions was determined according to the Palestinian Registered Product List and the Physician’s Desk Reference. Results Overall, 917 drug prescriptions were administered to 387children. Of all drug prescriptions, 528 (57.5%) were licensed for use in children; 65 (7.1%) were unlicensed; and 324 (35.3%) were used off-label. Of all children, 49.6% received off-label prescriptions, 10.1% received unlicensed medications and 8.2% received both. Seventy-two percent of off-label drugs and 66% of unlicensed drugs were prescribed for children \2 years. Multivariate analysis showed that patients who were admitted to the neonatal intensive care unit and infants aged 0–1 years were most likely to receive a greater number of off-label or unlicensed medications (OR 1.80; 95% CI 1.03–3.59 and OR 1.99; 95% CI 0.88–3.73, respectively). Conclusion The present findings confirmed the elevated prevalence of unlicensed and off-label paediatric drugs use in Palestine and strongly support the need to perform well designed clinical studies in children.
Genetic, serological and biochemical characterization of Leishmania tropica fromfoci in northern Palestine and discovery of zymodeme MON-307
(Springer, 2012-06-18) Abdelmajeed Nasseraldeen; Kefaya Azmi; Schnur, Lionel; Pratlong, Francine; Baidouri, Fouad; Ravel, Christophe; Dedet, Jean-Pierre; Ereqat, Suheir; Abdeen, Ziad; Schonian, Gabriele
Background: Many cases of cutaneous leishmaniasis (CL) have been recorded in the Jenin District based on their clinical appearance. Here, their parasites have been characterized in depth. Methods: Leishmanial parasites isolated from 12 human cases of CL from the Jenin District were cultured as promastigotes, whose DNA was extracted. The ITS1 sequence and the 7SL RNA gene were analysed as was the kinetoplast minicircle DNA (kDNA) sequence. Excreted factor (EF) serotyping and multilocus enzyme electrophoresis (MLEE) were also applied. Results: This extensive characterization identified the strains as Leishmania tropica of two very distinct sub-types that parallel the two sub-groups discerned by multilocus microsatellite typing (MLMT) done previously. A high degree of congruity was displayed among the results generated by the different analytical methods that had examined various cellular components and exposed intra-specific heterogeneity among the 12 strains. Three of the ten strains subjected to MLEE constituted a new zymodeme, zymodeme MON-307, and seven belonged to the known zymodeme MON-137. Ten of the 15 enzymes in the profile of zymodeme MON-307 displayed different electrophoretic mobilities compared with the enzyme profile of the zymodeme MON-137. The closest profile to that of zymodeme MON-307 was that of the zymodeme MON-76 known from Syria. Strains of the zymodeme MON-307 were EF sub-serotype A2 and those of the zymodeme MON-137 were either A9 or A9B4. The sub-serotype B4 component appears, so far, to be unique to some strains of L. tropica of zymodeme MON-137. Strains of the zymodeme MON-137 displayed a distinctive fragment of 417 bp that was absent in those of zymodeme MON-307 when their kDNA was digested with the endonuclease RsaI. kDNA-RFLP after digestion with the endonuclease MboI facilitated a further level of differentiation that partially coincided with the geographical distribution of the human cases from which the strains came. Conclusions: The Palestinian strains that were assigned to different genetic groups differed in their MLEE profiles and their EF types. A new zymodeme, zymodeme MON-307 was discovered that seems to be unique to the northern part of the Palestinian West Bank. What seemed to be a straight forward classical situation of L. tropica causing anthroponotic CL in the Jenin District might be a more complex situation, owing to the presence of two separate sub-types of L. tropica that, possibly, indicates two separate transmission cycles involving two separate types of phlebotomine sand fly vector.
Hippocampal BOLD Response During Category Learning Predicts Subsequent Performanceon Transfer Generalization
(Wiley Periodicals, Inc., 2014-10-13) Fera, Francesco; Passamonti, Luca; Myers, Catherine E.; Veltri, Pierangelo; Morganti, Giuseppina; Quattrone, Aldo; Gluck, Mark A.; Herzallah, Mohammad
To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands.
Impact of pharmaceutical care on health outcomes in patients with COPD
(Springer Science+Business Media B.V. 2011, 2011-11-20) Khdour, Maher; Jarab, Anan; AlQudah, Salam; Shamssain, Mohammed; Mukattash, Tareq
Background Chronic obstructive pulmonary disease (COPD) treatment goals are often not achieved despite the availability of many effective treatments. Furthermore, clinical pharmacist interventions to improve clinical and humanistic outcomes in COPD patients have not yet been explored and few randomized controlled trials have been reported to evaluate the impact of pharmaceutical care on health outcomes in patients with COPD. Objective The aimof the present studywas to evaluate the impact of pharmaceutical care intervention,with a strong focus on self-management, on a range of clinical and humanistic outcomes in patients with COPD. Setting Outpatient COPD Clinic at the Royal Medical Services Hospital. Method In a randomised, controlled, prospective clinical trial, a total of 133 COPD patients were randomly assigned to intervention or control group. A structured education about COPD and management of its symptoms was delivered by the clinical pharmacist for patients in the intervention group. Patientswere followed up at 6 months during a scheduled visit. Effectiveness of the intervention was assessed in terms of improvement in health-related quality of life,medication adherence, disease knowledge and healthcare utilization. Data collected at baseline and at the 6 month assessment was coded and entered into SPSS software version 17 for statistical analysis. A P value of\0.05 was considered statistically significant. Main outcome measure The primary outcome measure was health-related quality of life improvement. All other data collected including healthcare utilization, COPD knowledge and medication adherence formed secondary outcome measures. Results A total of 66 patients were randomized to the intervention group and 67 patients were randomized to the control group. Although the current study failed to illustrate significant improvement in health-related quality of life parameters, the results indicated significant improvements in COPD knowledge (P\0.001), medication adherence (P\0.05), medication beliefs (P\ 0.01) and significant reduction in hospital admission rates (P\0.05) in intervention patients when compared with control group patients at the end of the study. Conclusion The enhanced patient outcomes as a result of the pharmaceutical care programme in the present study demonstrate the value of an enhanced clinical pharmacy service in achieving the desired health outcomes for patients with COPD.
Increased Prevalence of Human Cutaneous Leishmaniasis in Israel and The Palestinian Authority Caused by the Recent Emergence of a Population of Genetically Similar Strains of Leishmania tropica
(Elsevier, 2016-08-05) Azmi, Kifaya; Krayter, Lena; Nasereddin, Abedelmajeed; Ereqat, Suheir; Schnur, Lionel; Al-Jawabreh, Amer; Abdeen, Ziad; Schonian, Gabriele
Twelve unlinked microsatellite markers were used to determine the microsatellite profiles of 50 newly and 46 previously typed strains of L. tropica from various Israeli and Palestinian foci. Their microsatellite profiles were compared to those of 99 previously typed strains of L. tropica from 15 countries. Israeli and Palestinian strains of L. tropica fell into three different groups, one of which contained 75 of the 96 Israeli and Palestinian strains. This population separated fromall the others at the first hierarchical level by Bayesian statistics and formed a distinct monophyletic group on applying genetic distance and allele frequency analyses. The second cluster contained ten Israeli strains from a specific focus north of the Sea of Galilee,whichwere previously shown to differ from all other strains of L. tropica in their serological, biochemical and molecular biological parameters. This clusterwas closely related to clusters comprising strains of L. tropica from Africa. Four Israeli and five Palestinian strains fell into different genetic entities mostly related to strains from Asian foci of CL. Importation during numerous migrations of humans and, perhaps, infected reservoir animals in the past and, now, through modern travel is the most likely explanation for the existence of so many locally encountered genetic variants of L. tropica in the Israeli-Palestinian region. Geographical and ecological variation may play a role in expanding the genetic heterogeneity once given importations had become established in different foci. Currently, one population is expanding in the area comprising almost all of the Palestinian and Israeli strains of L. tropica isolated since 1996 and investigated in this study, which differ clearly from all other strains ofwhatsoever origin. This population seems to result from the re-emergence of a previously existing genotype owing to environmental changes and human activities.
Learning from negative feedback in patients with major depressive disorder is attenuated by SSRI antidepressants
(2013-09-23) Herzallah, Mohammad M.; Moustafa, Ahmed A.; Natsheh, Joman Y.; Abdellatif, Salam M.; Taha, Mohamad B.; Tayem, Yasin I.; Sehwail, Mahmud A.; Amleh, Ivona; Petrides, Georgios; Myers, Catherine E.; Gluck, Mark A.
One barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs. learning from negative feedback (punishment). Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject's relative sensitivity to positive vs. negative feedback showed that both the medicated MDD and HC groups conform to Kahneman and Tversky's (1979) Prospect Theory, which expects losses (negative feedback) to loom psychologically slightly larger than gains (positive feedback). However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not "normal" when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the cognitive consequences of MDD from those of SSRI treatment, and from cognitive evaluation of MDD subjects in a medication-naïve state before the administration of antidepressants. Future research is needed to correlate the mood-elevating effects and the cognitive balance between reward- and punishment-based learning related to SSRIs.