Cognitive behaviour therapy for white coat hypertension-causing latrophobia in adults: randomized controlled trial.

OBJECTIVE: To see whether cognitive behaviour therapy improves blood pressure-oriented latrophobia in adults to manage white coat hypertension. METHODS: Present study was conducted at the Kidney Centre, Sialkot, Pakistan from December 2017 to November 2018, and comprised latrophobic attendees of kidney patients without initially exploring the reason of phobia. Either of the intervention or control group was allotted, randomly. The intervention group underwent 20 weekly sessions of the therapy. Pre- and posttherapy systolic blood pressure (at home and medical clinic) of both the groups was recorded alongside self-perceived level of phobia in subjects of only treatment group. RESULTS: Of 30 subjects of intervention group, 22 (73.3%) completed the therapy. However, control (N = 30) stayed intact. Age statistics were, as: M = 38.2, SD = 11.8, range 20-56 years with male predominance. Moreover, 12 (54.4%) or 20 (90.9%) of them reported severe latrophobia or onset of phobia after childhood, respectively. After therapy, 17 (77.3%) subjects communicated improvement in fear. A significant decline in mean systolic blood pressure was noted in pre- to posttherapy record (149 vs.142 mm of Hg, respectively; t(21)= 8.829, p = 0.0001). CONCLUSION: Generally, cognitive behaviour therapy improves blood pressure-oriented latrophobia in adults.

A VIKOR based approach for assessing the social, environmental and economic effects of "smog" on human health.

Nowadays, the excessive industrialization, increased use of fossil fuels, elevated levels of vehicular emissions are causing high level of air pollution reaching epidemic levels. The effects of "smog" or in other words of air pollution can be very dangerous for humans, and plants. In fact, air pollution can be linked to many health-related issues, as it is one of the leading causes of pulmonary, respiratory and skin diseases across the globe. In this context, Pakistan being an underdeveloped country, faces the hazardous impacts of smog on health, environment, transportation and educational sectors. The aim of the present research was to establish a correlation between smog/air pollution (the independent variable) and different dependent variables. The final goal was to define different precautionary measures and find their practicality and selection. Fuzzy VIKOR, a multi-criteria decision-making tool, was proposed in this research. It was applied to select an optimal alternative based on closeness to positive-ideal solution and deviation from the negative-ideal solution. Through this research, an environmental-friendly and health-promoting policy can be reach. This research will also help government in making future policies regarding environmental and industrial pollution. A case study settled in Pakistan was used to demonstrate the effectiveness of the proposed fuzzy model.

Synthesis, characterization and antihypertensive activity of 2-phenyl substituted benzimidazoles.

Hypertension is one of cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. Hypertension resulted in significant morbidity and mortality. The benz-imidazole ring is very important pharmacophore in modern drug discovery. The substituted benzimidazoles are the important for medicinal research. Researchers have reported that substituted Benzimidazoles are the structural isosteres of nucleotides, and easily allow them to interact with the different biopolymers, possess pharmacological activity especially antihypertensive activity. Angiotensin II Receptor Antagonists/Blockers (ARBs) compete with angiotensin II at the receptor site and block the contractile effect of angiotensin II in all vascular smooth muscles. Among all Angiotensin II Receptor Antagonists/Blockers (ARBs), Telmisartan, Milfasartan and many others have benzimidazole ring in their structure. In this study Angiotensin II Receptor Antagonists/Blockers (ARBs) have been prepared. Synthesized compounds were characterized by physical data and FTIR spectroscopic technique. Synthesized compounds studied were finally screened for their antihypertensive activity by tail cuff method of measurement of blood pressure by NIBP apparatus (None Invasive Blood Pressure) using Chart 5.0 software. The compounds synthesized were 2-(3-nitrophenyl)-1Hbenzimidazole (1a), 3-(1H benzimidazol-2-yl)aniline (1b) and 5-(1H-benzimidazol-2-yl)-2-methoxyphenol (1c). The synthesized compounds have shown antihypertensive activity by taking Losartan as lead compound.

Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study.

We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site.

Synthesis, characterization and evaluation of lecithin-based nanocarriers for the enhanced pharmacological and oral pharmacokinetic profile of amphotericin B.

We report the synthesis, characterization and evaluation of lecithin-drug hybrid nanocarriers (NCs) with enhanced oral bioavailability and anti-parasitic potential for poorly water-soluble drugs. Amphotericin B (AmB), a poor water-soluble drug with poor membrane penetrating ability, was selected as a model drug to demonstrate the potential of the lecithin-drug hybrid NCs. Lec-AmB NCs were prepared by the self-assembly of lecithin into nanoparticles (NPs) at a critical micellar concentration of 4 mg ml-1 and into liposomes at a critical liposomal concentration of 53 mg ml-1 in aqueous systems. The Lec-AmB NPs (200-300 nm) were further coated with polyethylene glycol (MW 600) and Tween 20, whereas the liposomes (70-90 nm) were used as such for this study. The Lec-AmB NCs were evaluated for their ability to boost in vivo oral pharmacokinetic parameters in rabbits and in vitro anti-leishmanial activity against the promastigotes of Leishmania tropica. A reciprocal relationship was observed between the size and drug encapsulation efficiency of the NPs, but no such relationship was observed in the case of the liposomes. More importantly, the oral bioavailability and anti-leishmanial activity of Lec-AmB NPs was enhanced up to 21- and 6.3-fold, and 21- and 2-fold, respectively, in the case of the liposomes. The improvement in the bioavailability and anti-leishmanial activity is very significant compared to the deoxycholate complex of AmB (water soluble, injectable market product: Anfotericina FADA®), and this study, thus shows the promising potential of easy-to-prepare NCs with improved therapeutic efficiency using phosphocholine-based biocompatible surfactants.

Improved physicochemical characteristics of artemisinin using succinic acid.

Artemisinin (ARMN) is a potent antimalarial drug, which is effective against multidrug resistant strains of Plasmodium falciparum and produces rapid recovery even in patients with cerebral malaria. Being poorly soluble in water, artemisinin is incompletely absorbed after oral intake due to poor dissolution characteristics in the intestinal fluids. To enhance these properties, solid dispersions of artemisinin with succinic acid (SUC) were prepared using drug-carrier ratios 1 : 1, 1 : 4, 1 : 6, 1 : 8 and 1 : 10 by solvent evaporation and freeze drying methods. These solid dispersions were characterized by differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), x-ray diffraction patterns (XRD), phase solubility and dissolution kinetics evaluated by applying zero order, first order, Higuchi, and Korsmeyer-Peppas models. Physical mixtures produced significantly higher aqueous solubility and rate of dissolution as compared to artemisinin alone. The dissolution profiles of all formulations followed Higuchi model and exhibited diffusion-controlled release of drug. Solvent evaporation method (SLVPs) exhibited improved solubility and freeze dried solid dispersions (FDSDs) produced highest solubility but stability constant was opposite. ARMN and SUC both were found completely crystalline as shown by their XRD patterns. Physical mixtures (PMs) showed reduced intensity in their XRD patterns while solid dispersions by SLVPs exhibited twice reduced intensity and much displaced angles, whereas FDSDs showed synergistic effects in some of ARMN and SUC peaks. DSC thermograms of FDSDs at drug-carrier ratios 1 : 1-1 : 4 showed lower melting temperature and enthalpy change (deltaH) values than respective SLVPs, whereas at higher ratios, a reverse was true. SLVPs showed displaced methyl stretching bands at lower drug-carrier ratios and exhibited O-H stretching characteristic bands of SUC at higher drug-carrier ratios. In addition, carbonyl group and C-O stretching vibrations characteristic of SUC (1307 cm(-1)) appeared prominently compared to PMs, whereas C-O stretching characteristic bands of ARMN disappeared at higher ratios. FDSDs exhibited distinct nature of bonding compared to respective SLVPs and PMs.

Effect of ketoprofen on lactic dehydrogenase from human platelets.

BACKGROUND: In different clinical investigations of thrombocytopenia, ketoprofen was found to be the associated cause. Ketoprofen alone or in combination with other therapeutic regimens leads to a decrease in platelet count. Thrombocytopenia due to ketoprofen use can be a threatening condition to the patients who require uncompromised platelet function. OBJECTIVES: In order to establish a mechanism for thrombocytopenia associated with ketoprofen use, the enzyme inhibition effects of ketoprofen on lactic dehydrogenase (LDH) were investigated in this study. LDH is essentially involved in platelet energy production. MATERIAL AND METHODS: LDH isolated from human platelets was subjected to different concentrations of ketoprofen (250, 500, 750, 1000 and 1500 µg/mL) and pyruvate as a substrate (45, 60 and 90 µM/mL) to gain insight into the enzyme inhibition effects for forward reaction. Oxidation of nicotinamide adenine dinucleotide (NADH) was measured at 340 nm to evaluate enzyme activity. Enzyme inhibition kinetics were studied via Lineweaver Burk plot. RESULTS: Ketoprofen was found to be a competitive inhibitor of LDH in human platelets. 89% of enzyme activity was inhibited by a 1500 µg/mL concentration of the drug and the enzyme inhibition constant was 882 µg/mL. CONCLUSIONS: The possible main cause of thrombocytopenia due to ketoprofen use is LDH inhibition in platelets, which are essential for platelet energy metabolism. So patients who require uncompromised platelet function and are receiving ketoprofen in their prescription should be monitored for platelet count and blood clotting.

Detection of citrus huanglongbing-associated 'Candidatus Liberibacter asiaticus' in citrus and Diaphorina citri in Pakistan, seasonal variability, and implications for disease management.

We report the detection of the huanglongbing (HLB)-associated bacterium 'Candidatus Liberibacter asiaticus' from both plants and insects in Pakistan and the seasonal variability in the numbers of 'Ca. L. asiaticus'-positive psyllid vector, Diaphorina citri. Our studies showed that 'Ca. L. asiaticus' was detectable from trees in areas with maximum temperatures reaching nearly 50°C (average maximum of 42°C). However, the bacterium was present at very low levels in psyllids both in summer (June to August) and autumn (September to November) in contrast to reports from Florida, where the bacterium was detectable at very high levels during October to November. We hypothesize that hot summer temperatures in Pakistan may interfere with acquisition and replication of 'Ca. L. asiaticus' in psyllids and may lead to dead or non transmissible 'Ca. L. asiaticus' in plants. Psyllid counts were very low in both summer and winter, showed a population peak ('Ca. L. asiaticus'-positive vectors) in spring, and showed a larger peak ('Ca. L. asiaticus'-free psyllids) in autumn. Natural thermotherapy during hot summers and a low vector population during environmental extremes may have played a major role in long-term survival of the citrus industry in Pakistan. These results may be useful in developing management strategies for U.S. citrus industries in Texas and California.

Improved physicochemical characteristics of artemisinin-nicotinamide solid dispersions by solvent evaporation and freeze dried methods.

Artemisinin (ARMN) is a drug of choice against drug-resistant malaria especially due to Plasmodium falciparum. Being poorly soluble in water, its solid dispersions with nicotinamide (NA) were prepared at various drug-carrier ratios (1:1, 1:4, 1:6, 1:8, 1:10) by solvent evaporation and freeze drying methods. These solid dispersions were characterized by differential scanning calorimetery (DSC), fourier transform infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), phase solubility and dissolution studies. Artemisinin and nicotinamide both were found completely crystalline as shown by their XRD patterns. Physical mixtures (PMs) showed decreased intensity in their XRD patterns while solid dispersions by solvent evaporation method (SLVPs) exhibited displaced angles and decreased intensity whereas freeze dried solid dispersions (FDSDs) showed least number of peaks having low intensity and maximum displaced angles. DSC thermograms of drug-carrier ratios at 1:1-1:4 showed lower melting temperature than artemisinin and nicotinamide in all preparations. Endothermic temperature of artemisinin in PMs and SLVPs increased with rise of nicotinamide content upto 1:6 ratio followed by decline. All samples showed crystallization temperature below the artemisinin except drug-carrier ratio 1:6 of PMs while δH value was minimum at this ratio. FDSDs produced lowest endothermic temperature than corresponding PMs and SLVPs. SLVPs exhibited band shifting in both functional and fingerprint region compared to respective PMs as exhibited by their FTIR spectra. FDSDs and SLVPs showed different nature of bonding among artemisinin and nicotinamide. FDSDs produced strongest CONH(2) bonding followed by SLVPs and PMs respectively. PMs produced significantly higher aqueous solubility and rate of dissolution as compared to artemisinin alone. SLVPs exhibited improved solubility and dissolution profile corresponding to PMs. FDSDs showed highest release rate and aqueous solubility followed by SLVPs and PMs at all ratios. PMs and SLVPs showed their highest dissolution profile at 1:6 drug-carrier ratio followed by gradual decrease while FDSDs progressed in dissolution rate with increase of nicotinamide content successively upto maximum at 1:10 ratio.

Coagulopathies in Naja naja karachiensis (black Pakistan cobra) bites and its effect on coagulation tests upon storage of platelet-poor plasma.

The aim of this study was to evaluate the effect of venom from Naja naja karachiensis on platelet-poor plasma, activated partial thromboplastin time (aPTT), prothrombin time (PT) / international normalized ratio (INR), thrombin time (TT) and to evaluate its effect on clotting time upon storage of plasma for a specific time period with possible mechanism responsible for that. Prolongation of PT / INR, aPTT and TT was observed when different concentrations of venom were introduced due to degeneration of fibrinogen. Preservation of plasma for three months further prolong clotting time for coagulation tests, however, difference of PT and TT results were not very prominent as compared to aPTT. Minute concentrations of cobra venom and short as well as long storage of platelet-poor plasma badly affects the INR ratio.

Antihaemorrhagic potentials of Fagonia cretica against Naja naja karachiensis (black Pakistan cobra) venom.

Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this study was to determine the antivenom potentials of methanolic extract from the aerial parts (leaves and twigs) of Fagonia cretica L. on a haemorrhage induced by venom from Naja naja karachiensis. The haemorrhagic response of venom was dose dependent from 0.1 to 4.0 µg per 1.5 µL phosphate buffer saline (PBS) on vitelline veins of fertilised hens' eggs in their shells. The extract effectively eliminated and neutralised, in a dose-dependent manner, the haemorrhagic activity of snake venom. The minimum effective neutralising dose of F. cretica extract was found to be 15 µg per 1.5 µL PBS. The extract possesses potentials as haemorrhagic inhibitor against snake venom compared to the standard antiserum and various plants reported in the literature. This study also provides a scientific base for the use of F. cretica in traditional medicine for the treatment of snake bite.

Impact of alterations in teaching methodologies on learning capabilities.

OBJECTIVE: To compare the role of new approaches and methods in the development of understanding and learning capabilities of undergraduate medical students in the module of respiratory physiology. METHODS: A comparative cross sectional study was conducted in Bahria Univiersity Medical & Dental College using a sample size of 198 students from February till May 2010. Difficulties in understanding the concepts of respiratory physiology was analyzed in groups A (Batch 2008-2013) and assessed through test performance. In group B (Batch 2009-2014) "integrated learner-and teacher-centered" approach was implemented by introduction of problem based learning, case based sessions, students seminar, quizzes and structured assignments. Response of group B students was evaluated in terms of concepts and performance by identical feedback form and assessment test. The data was analyzed using SPSS version 15.0 and applying the Chi-square test. RESULTS: The mean age of Karachi students of Groups A and B was 20 +/- 2 years. Statistically significant improvement in conceptual understanding of Group B (84%) was noticed compared to Group A (42%). Conceptual understanding of Group B (84%) was observed, as compared to Group A (42%) CONCLUSION: Supplementation of teaching methodologies with augmented interaction improved significant learning, performance and satisfaction among group B students.

Synergism between collagen-adenosine diphosphate and collagen-epinephrine in platelets' aggregation: different dose response relationships.

OBJECTIVES: To evaluate the possible synergistic interaction of collagen-adenosine diphosphate and collagen-epinephrine in aggregation of human platelets. METHODS: An experimental study was carried out at Armed Forces Instiute of Pathology, Rawalpindi, Pakistan, from June 2001 to December 2002. The platelet aggregation was determined by means of turbidometric method, which measures changes in optical density of platelet suspension. After determining the sub-threshold values of each agonist with the help of dose-response curve, these agonists were added in pairs to determine the synergism between them. RESULTS: The differences between means of threshold and sub-threshold concentrations of agonists were significant (Collagen: P<0.001, ADP: P<0.001, Epinephrine: P<0.002). The responses of Collagen and Epinephrine in sub-threshold concentrations were synergistic in causing platelet aggregation, whereas there were no potentiating effects in response to that of Collagen and Adenosine diphosphate. CONCLUSION: The study reveals the synergistic potentiation of some of the agonists in circulation that might be responsible for the activated state of platelets and associated atherosclerotic complications.

The Community Health Information System (CHIS): delivering web-based customised healthcare using an AI-infused expert system.

The Community Health Information System (CHIS) is an integrated, patient-centric, web-based application that assists all stakeholders in healthcare management. CHIS is a single sign-on portal that allows users to query an immense interconnected database of medical research, healthcare providers, regulations, nurses and physicians. A three member faculty team at Western Michigan University has developed a system prototype using a collection of technologies to deliver the content via a variety of interfaces such as the web, mobile devices, voice and kiosks. The focus of this paper is on the technical building blocks such as decision-making process, system models and functional components.

Comparison of lipid profiles and lipoprotein a levels in patients with type 2 diabetes mellitus during oral hypoglycemic or insulin therapy.

OBJECTIVE: The aim of this study is to compare lipid and lipoprotein (a) profiles in patients with type 2 diabetes mellitus (DM) on insulin and oral hypoglycemic therapy. METHODS: The study took place in the Department of Physiology, Army Medical College, Rawalpindi, Pakistan, during 2002. Ninety-seven type 2 DM patients participated in the study. We divided the patients according to the type of treatment into sulphonylurea (n=40), sulphonylurea plus metformin (n=33) and insulin (n=24) therapy groups as well as 40 healthy subjects served as controls. Fasting blood samples were analyzed for lipoprotein (a) [Lp (a)], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, glycosylated hemoglobin (HbA1c) and insulin. RESULTS: Different groups of diabetic patients showed elevated fasting blood glucose (FPG) levels (p<0.0001 for all), HbA1c (p<0.0001 for all) compared with controls. Meanwhile, fasting insulin levels were elevated only in insulin treated group compared with oral hypoglycemic treated groups and controls (p<0.0001 for all). Patients on sulphonylurea and on sulphonylurea plus metformin groups showed significantly elevated TC (p<0.001, p<0.0001), TG (p<0.001, p<0.01), LDL-C (p<0.01, p<0.001) and LDL-C/HDL-C (p<0.0001, p<0.0001) compared with controls. Insulin therapy group showed significantly decreased TC, TG, LDL-C, LDL-C/HDL-C levels compared with sulphonylurea and sulphonylurea plus metformin treated groups, however, no significant difference was noted in the levels of above mentioned parameters and controls. Meanwhile, HDL-C levels were significantly lower in all diabetic groups compared with controls and were higher in insulin treated group compared with sulphonylurea plus metformin therapy group (p<0.05). Lipoprotein (a) levels were significantly higher in different diabetic groups compared with controls. While there was a non-significant difference in Lp (a) levels between different diabetic groups. CONCLUSION: Patients with type 2 DM who are being treated on insulin have a better lipid profile (TC, HDL-C, LDL-C, TG) compared with those patients on oral hypoglycemic agents. Meanwhile, Lp (a) levels were raised in all diabetic patients and seem not to be affected either by insulin or by oral hypoglycemic treatment.

Synergistic interaction of adenosine diphosphate-epinephrine and epinephrine-collagen in aggregation of human platelets.

BACKGROUND: Efficient hemostasis in human body depends on a complicated series of events which actively involve blood platelets. Platelets exhibit diverse responses in a variety of agonists. In vivo, most of the agonists act in synergism, causing aggregation of platelets. METHODS: In this study, the synergism between ADP-Epinephrine and Epinephrine-Collagen has been determined by means of turbidometric method, which measures changes in optical density of platelet suspension. The study was carried out at the department of Hematology, Armed Forces Institute of Pathology, Rawalpindi. The subthreshold concentrations of each of the agonists were established with the help of dose response curve. By adding these agonists in subthreshold concentrations, the synergism between ADP-Epinephrine and Epinephrine-Collagen was determined. RESULTS: The combinations of these agonists in subthreshold levels showed the synergistic responses in causing platelet aggregation. CONCLUSION: These findings indicate that the optimal platelet aggregation does occur between the above mentioned pairs of agonists even when each of the agonist is added to the other in subthreshold doses.