Bentham Science Publishers

Aim: To investigate the association between selection bias - established by use of the I2 test from published randomised controlled trials (RCTs) and the effect estimate magnitude of these trials. Two null-hypotheses were tested: H01 - The magnitude of trial effect estimates is not significantly positively correlated with the identified selection bias levels and H02 - The magnitude of trial effect estimates does not differ significantly between RCTs with identified ‘low’ and ‘high’ selection bias.
Methods: RCTs reporting computable outcome and baseline data were selected from published systematic review reports that, in turn, were identified through a systematic literature search in PubMed up to 2024. All RCTs were tested for selection bias using the trial adjusted, SCT based I2 test. For each RCT, the selection bias level (B%) was determined, and the absolute value of the risk difference (RD) point estimate was calculated. H01 was tested using Spearman’s rank correlation, and H02 was tested using an independent samples t-test. A sensitivity analysis was carried out to examine any potential confounder effect.
Results: A total of 332 RCTs, published from 1985 – 2023 in various medical specialties, were tested.  ‘Low’ selection bias was identified in 202 RCTs and ‘high’ selection bias in 130 RCTs. There was a significant positive correlation between the magnitudes of trial effect estimates and the selection bias levels (Spearman’s rho = 0.304, p < 0.0001). The effect estimates were statistically significantly higher (0.094; 95%CI: 0.075 – 0.11; p < 0.0001) for RCTs with identified ‘high’ selection bias than for RCTs with ‘low’ selection bias. The effect size over-estimation in RCTs with ‘high’ selection bias, compared to trials with ‘low’ bias was 8.1 (95%CI: 7.5 – 11.0) percentage points, representing a proportional over-estimation of 86% (95%CI: 80-92%). Both null-hypotheses H01 and H02 were rejected.
Conclusion: The trial adjusted, SCT based I2 test proved to be effective for identifying high-level selection bias in RCTs. The test allowed estimation of the selection bias extent and its possible effect on the reported trial effect estimate

Cyanovirin-N (CV-N), a cyanobacterial lectin, is a potent viral entry inhibitor currently under development as a microbicide against a broad spectrum of enveloped viruses. CV-N was originally identified as a highly active anti-HIV agent and later, as a virucidal agent against other unrelated enveloped viruses such as Ebola, and possibly other viruses. CV-N's antiviral activity appears to involve unique recognition of Nlinked high-mannose oligosaccharides, Man-8 and Man-9, on the viral surface glycoproteins. Due to its distinct mode of action and opportunities for harnessing the associated interaction for therapeutic intervention, a substantial body of research on CV-N has accumulated since its discovery in 1997. In this review we focus in particular on structural studies on CV-N and their relationship to biological activity.

The systolic ratio of a contact form on a closed three-manifold is the quotient of the square of the shortest period of closed Reeb orbits by the contact volume. We show that every co-orientable contact structure on any closed three-manifold is defined by a contact form with arbitrarily large systolic ratio. This shows that the many existing systolic inequalities in Finsler and Riemannian geometry are not purely contact-topological phenomena.

Melanoma is the most aggressive type of skin cancer due to its high capability of developing metastasis and acquiring chemoresistance. Altered redox homeostasis induced by increased reactive oxygen species is associated with melanomagenesis through modulation of redox signaling pathways. Dysfunctional endothelial nitric oxide synthase (eNOS) produces superoxide anion (O2−•) and contributes to the establishment of a pro-oxidant environment in melanoma. Although decreased tetrahydrobiopterin (BH4) bioavailability is associated with eNOS uncoupling in endothelial and human melanoma cells, in the present work we show that eNOS uncoupling in metastatic melanoma cells expressing the genes from de novo biopterin synthesis pathway Gch1, Pts, and Spr, and high BH4 concentration and BH4:BH2 ratio. Western blot analysis showed increased expression of Nos3, altering the stoichiometry balance between eNOS and BH4, contributing to NOS uncoupling. Both treatment with L-sepiapterin and eNOS downreg...

OBJETIVO: Avaliar o impacto da integridade da cortical lateral osteo-tomia alta de tíbia (OAT) com cunha de abertura. MÉTODOS: Modelos experimentais artificiais em poliuretano foram fixados com placa DCP® 4,5mm. Cunhas de abertura foram confeccionadas para simular a distração da osteotomia alta da tíbia. Realizadas falhas na cortical lateral para simular fraturas e fixadas com diferentes tipos de parafusos. Ensaios de torção e compressão axial foram realizados. 04 diferentes grupos foram constituídos. RESULTADOS: As medidas de torção registradas no grupo com cortical íntegra foram superiores àquelas obtidas no grupo com cortical rompida (p&lt;0,001) e estatisticamente equivalentes aos grupos com cortical rompida associado à parafuso de estabilização lateral de compressão ou de posição (p&gt;0,05). As medidas de compressão obtidas no grupo com cortical íntegra foram superiores aos demais grupos (p&lt;0,001). Em torção e compressão não houve diferença estatística entre os tipos de par...

Purpose: The primary goal of this study was to compare survivorship and functional results in individuals aged 80 and over who underwent total knee arthroplasty (TKA) with cruciate-retaining (CR) or posterior-stabilized (PS) implants. Methods: We prospectively analyzed the clinical records of two consecutive cohorts for a total of 96 implants in patients aged 80 years or over. The first cohort consisted of 59 consecutive cemented PS cases, while the second cohort comprised 37 consecutive cemented CR cases. The decision to either perform a PS or CR arthroplasty was taken based on preoperative magnetic resonance imaging and intraoperative findings. The clinical evaluation entailed evaluating each patient’s visual analogue scale for pain (VAS), range of motion (flexion and extension), Knee Society Score (KSS), and Oxford Knee Score (OKS). Each patient was clinically evaluated the day before surgery (T0) and at two consecutive follow-ups at least 1 (T1) and 2 (T2) years after surgery. I...

Biphalin (Tyr-D-Ala-Gly-Phe-NH-NH<-Phe<-Gly<-D-Ala<-Tyr) is an opioid octapeptide with a dimeric structure based on two identical pharmacophore portions, derived from enkephalins, joined "tail to tail" by a hydrazide bridge. This particular structure enhances the antinociceptive activity of the native enkephalins with an unknown mechanism, probably based on a cooperative binding and improved enzymatic stability. Biphalin has excellent binding affinity for μ and receptors and it is a highly potent analgesic, as potent as or more than ethorphine. A definitive explanation of the extraordinary in vivo potency shown by this compound, which has pronounced efficacy in pain modulation, is still not available; it has been suggested, however, that the high agonist activity may be related to its binding mode at both μ and opioid receptors. Biphalin has significantly higher potency than other analgesics with novel biological profiles; in particular, most recent data show that biphalin is unlikely to produce dependency in chronic use. In the past 20 years, there have been many attempts to modify its structure to obtain products unaffected by the action of enkephalinases, to enhance its antinociceptive activity and to modify the BBB penetration. In addition, structure-activity relationship studies (SAR) were performed in order to understand the elements responsible for biphalin's high activity. The aim of the studies reported in this review was to clarify: i) the role of the hydrazide bridge, ii) the role of residues in position 4, 4' and 3, 3', iii) the consequences of molecular simplifications (truncation, delection), iv) the consequences of cyclization through a disulfide bridge, v) conjugation with PEG and fluorescet residues, and vi) radiolabeling on Tyr 1 .

Some studies have indicated that human paraoxonase 1 (PON1) activity shows a polymorphic distribution. The aim of this study was to determine the distribution of PON1 polymorphism in patients with Alzheimer&#39;s disease in Gorgan and compare it with a healthy control group. The study included 100 healthy individuals and 50 patients. Enzyme activity and genetic polymorphism of PON1 were determined. There were significant differences in distribution of genotypes and alleles among patients and control group. The most common genotype was CT in patients and control group, while the most frequent alleles were T and C in patients and controls, respectively. There was a statistically significant variation between serum PON1 activity and -108C&gt; T polymorphism. The highest PON1 enzyme activities in the patients and controls were found in CC, while lower enzyme activities were seen in CT and TT genotypes in both genders and age groups. Onset of Alzheimer&#39;s disease may depend on differe...

This technical report demonstrates that the use of the I 2 statistic for testing selection bias in single randomised controlled trials (RCTs) has the potential to allow the prevention of false-positive test results, thereby allowing for high test specificity and a high positive predictive value. In addition, the I 2 statistic provides utility for the in-depth identification of low-level selection bias in RCTs, thus assisting in the avoidance of false-negative test results and possibly for estimating the percentage of trial patients with biased allocation into RCT treatment groups. Future studies to this topic may investigate whether cases with I 2 estimates above 0%, due to chance rather than selection bias, are possible and, if so, how to distinguish such cases from those with very low bias levels. Future studies may also test the null hypothesis that levels of selection bias are not associated with any over-or underestimation of the true effect estimates of RCTs.

This technical report demonstrates that the use of the I 2 statistic for testing selection bias in single randomised controlled trials (RCT) has the potential to allow prevention of false positive test results, thereby allowing for high test specificity and a high positive predictive value. Additionally, the I 2 statistic also provides utility for the in-depth identification of low-level selection bias in RCTs, thus assisting in the avoidance of false negative test results and possibly for estimating the percentage of trial patients with biased allocation into RCT treatment groups. Future studies to this topic may investigate whether cases with I 2 estimates above 0%, due to chance rather than selection bias, are possible and, if so, how to distinguish such cases from those with very low bias levels. Future studies may also test the null-hypothesis that levels of selection bias are not associated with any over-or under estimation of the true effect estimates of RCTs.

The authors present the results of the use of a hydroxyapatite coated custom made prosthesis, fixed to the bone through a side plate, without bone cement, in the treatment of primary bone tumors. They studied 15 patients between January 1995 to July 1998. The medium follow-up was 19.6 (6 to 42) months. Among the patients, 8 (53.3%) were males and 7 (46.7%) females. The medium age was 15.9 (7 to 31) years old. The diagnosis were osteosarcoma in 9 (60.0%) patients, Ewing sarcoma in 4 (26.7%), giant cell tumor and hemangiopericitoma in 1 (6.6%) each. Fourteen among the fifteen patients are alive and in follow-up. Among the complications there were two (12.3%) cases of breaking of the prosthesis, 1 (6.6%) case of infection and 1 (6.6%) case of local recurrence. The authors concluded that the non cemented custom made prosthesis, coated by hydroxyapatite and fixed to the bone through side plates are an important option to the treatment of primary bone tumors.

Vegetables are susceptible to diseases and pest attack; hence pesticides are widely used by farmers to avoid or reduce pests. The use of pesticides may leave some residues on the vegetables after harvesting and not safe for consumption. Thus, it is essential to monitor the levels and concentrations of pesticide residues in vegetables. Currently, gas chromatography and high-performance liquid chromatography are used as a method for detecting the components of pesticide residues in vegetables. However, these methods are destructive and often time consuming. Therefore, in this study, Fourier transform infrared (FT-IR) spectroscopy combined with multivariate data analysis was selected as a rapid, non-destructive method to obtain spectral information from pesticide residues. Spinach leaves were sprayed with malathion followed by washing treatments. The results showed that washed and non-washed samples can be clearly distinguished, with non-washed samples showing a high absorbance intensi...

The post-genomic era has completed its first decade. During this time, we have seen an attempt to understand life not just through the study of individual isolated processes, but through the appreciation of the amalgam of complex networks, within which each process can influence others. Greatly benefiting this view has been the study of the epigenome, the set of DNA and histone protein modifications that regulate gene expression and the function of regulatory non-coding RNAs without altering the DNA sequence itself. Indeed, the availability of reference genome assemblies of many species has led to the development of methodologies such as ChIP-Seq and RNA-Seq that have allowed us to define with high resolution the genomic distribution of several epigenetic elements and to better comprehend how they are interconnected for the regulation of gene expression. In the last few years, the use of these methodologies in the cardiovascular field has contributed to our understanding of the importance of epigenetics in heart diseases, giving new input to this area of research. Here, we review recently acquired knowledge on the role of the epigenome in heart failure, and discuss the need of an epigenomics roadmap for cardiovascular disease.

The post-genomic era has completed its first decade. During this time, we have seen an attempt to understand life not just through the study of individual isolated processes, but through the appreciation of the amalgam of complex networks, within which each process can influence others. Greatly benefiting this view has been the study of the epigenome, the set of DNA and histone protein modifications that regulate gene expression and the function of regulatory non-coding RNAs without altering the DNA sequence itself. Indeed, the availability of reference genome assemblies of many species has led to the development of methodologies such as ChIP-Seq and RNA-Seq that have allowed us to define with high resolution the genomic distribution of several epigenetic elements and to better comprehend how they are interconnected for the regulation of gene expression. In the last few years, the use of these methodologies in the cardiovascular field has contributed to our understanding of the importance of epigenetics in heart diseases, giving new input to this area of research. Here, we review recently acquired knowledge on the role of the epigenome in heart failure, and discuss the need of an epigenomics roadmap for cardiovascular disease.

Background: Several techniques have been used for the treatment of fractures in large animals, once these animals are frequently subject to trauma that interrupts bone continuity, especially in long bones. The choice for the technique depends on the configuration of the fracture, damage to the adjacent tissue, and presence or absence of bone exposure. The success of the modified Thomas splint, associated to synthetic casting has been reported in several studies. However, there still are restrictions to the use of this technique. Thus, the objective of the present study is to report the use of immobilization by the modified Thomas splint, coupled with synthetic casting, for the treatment of fractures in long bones of bovine and equine animals. Cases: The five animals were treated at the Veterinary Hospital of the Universidade Paranaense, being four bovines and one equine, all presenting fractures in long bones, resulting from accidental trauma. The equine, weighting 300 kg, presented...

Objective: To examine the psychometric properties of the Arthritis Body Experience Scale (ABES) in a US sample of people with osteoarthritis, rheumatoid arthritis, fibromyalgia and other rheumatic conditions. The ABES, with the scoring direction modified, was phone-administered to 937 individuals who self-identified as having one or more arthritis conditions based on a validated, US, national survey assessment tool. Descriptive statistics of demographic variables and factor analysis of scale items were conducted. Scale dimensionality was assessed using principal component analysis (PCA) with oblique rotation. Criteria for assessing factors were eigenvalues > 1, visual assessment of scree plot, and structure and pattern matrices. Results: The predominantly female (74.2%) and Caucasian (79.9%) sample had a mean age of 61.0 ± 13.1 years, and a mean BMI of 30.2 ± 7.1. Major arthritis conditions reported were rheumatoid arthritis, osteoarthritis and fibromyalgia. A three-factor structure with cronbach alpha values of .84, .85 and .53 was elicited, and accounted for 72% of the variance. Discussion: Compared to the two-factor structure evidenced by the original ABES scale in a sample of UK adults, the data from this sample evidenced a three-factor structure with higher variance. The third factor's cronbach alpha of .53 was low and could be improved by the addition of salient questions derived from further qualitative interviews with patients with arthritis and other rheumatic conditions and from current literature findings. The observed psychometrics indicate the scale usefully assesses body image in populations with arthritis and related conditions. However, further testing and refinement is needed to determine its utility in clinical and other settings.

Background: Pedestrians and vehicles are the two most important elements in designing roads and highways. However, for a long time, the designer focused on vehicle issues and did not give sufficient attention to pedestrian safety. Recently though, pedestrians have become the subject of much research and many studies. Moreover, most transportation codes include specific considerations and standards for pedestrians. One of the main pedestrian issues considered in facilities and traffic signal design is pedestrian walking speed. It is, therefore, necessary to evaluate the walking speed change patterns at crosswalks and the appropriate design walking speed for pedestrians, which can then be used to design pedestrian facilities and traffic signals. Methods: In this study, the crossing speeds of 4,301 pedestrians were collected from six different locations in Nablus, the second-most populous city in Palestine. Three of these locations were at unsignalized crosswalks, and the other three l...

Background: Several techniques have been used for the treatment of fractures in large animals, once these animals are frequently subject to trauma that interrupts bone continuity, especially in long bones. The choice for the technique depends on the configuration of the fracture, damage to the adjacent tissue, and presence or absence of bone exposure. The success of the modified Thomas splint, associated to synthetic casting has been reported in several studies. However, there still are restrictions to the use of this technique. Thus, the objective of the present study is to report the use of immobilization by the modified Thomas splint, coupled with synthetic casting, for the treatment of fractures in long bones of bovine and equine animals. Cases: The five animals were treated at the Veterinary Hospital of the Universidade Paranaense, being four bovines and one equine, all presenting fractures in long bones, resulting from accidental trauma. The equine, weighting 300 kg, presented...

A solution treatment of 1 hour at 540 o C provided the best results for rheocast alloy A356-T6. Natural aging has a significant influence on the subsequent artificial aging response of the alloy. Arrhenius-type equations were derived to predict the time-to-peak hardness as a function of artificial aging temperature.

A solution treatment of 1 hour at 540 o C provided the best results for rheocast alloy A356-T6. Natural aging has a significant influence on the subsequent artificial aging response of the alloy. Arrhenius-type equations were derived to predict the time-to-peak hardness as a function of artificial aging temperature.

A solution treatment of 1 hour at 540 o C provided the best results for rheocast alloy A356-T6. Natural aging has a significant influence on the subsequent artificial aging response of the alloy. Arrhenius-type equations were derived to predict the time-to-peak hardness as a function of artificial aging temperature.

Neurological disorders constitute a growing worldwide concern due to the progressive aging of the population and the risky behavior they represent. Herbal medicines have scientific relevance in the treatment of these pathologies. One of these substances, Astragaloside IV (AS-IV), is the main active compound present in the root of Astragalus membranaceus (Fisch.) Bge, a Chinese medicinal herb with neuroprotective properties. &lt;/p&gt; &lt;p&gt; Objective: In the present study we performed a systematic review that sought to comprehend the neuroprotective effect presented by AS-IV in experimental models of neurological disorders. &lt;/p&gt; &lt;p&gt; Method: This study is a systematic review, where an electronic search in United States National Library of Medicine (PubMed), Science Direct, Cochrane Library, Scientific Electronic Library Online (SciELO), Scopus, Web of Science, Medline via Proquest and Periodicos Capes databases covering the years between 2007 and 2017, using &quot;Ast...

Neurological disorders constitute a growing worldwide concern due to the progressive aging of the population and the risky behavior they represent. Herbal medicines have scientific relevance in the treatment of these pathologies. One of these substances, Astragaloside IV (AS-IV), is the main active compound present in the root of Astragalus membranaceus (Fisch.) Bge, a Chinese medicinal herb with neuroprotective properties. &lt;/p&gt; &lt;p&gt; Objective: In the present study we performed a systematic review that sought to comprehend the neuroprotective effect presented by AS-IV in experimental models of neurological disorders. &lt;/p&gt; &lt;p&gt; Method: This study is a systematic review, where an electronic search in United States National Library of Medicine (PubMed), Science Direct, Cochrane Library, Scientific Electronic Library Online (SciELO), Scopus, Web of Science, Medline via Proquest and Periodicos Capes databases covering the years between 2007 and 2017, using &quot;Ast...

Background and Objectives: Helicobacter pylori (H.pylori) colonize the human gastric and duodenal mucosa, and the infection may cause peptic ulcers and gastritis. Most studies indicated that Helicobacter pylori infection affects micronutrients zinc and copper. The objective of the study wasto compare serum concentration of trace elements zinc (Zn) and copper (Cu) of gastritis Helicobacter pylori-Infected patientswith those of gastritis H.pylori negative. : This was cross sectional case control study. The study was conducted in 40 gastritis H.pylori-infected patients and 40 (age and gender) matched gastritis H.pylori negative control. Stool Antigen H.pylori test was used to determine H.pylori, and Flame Atomic Absorption Spectroscopymethod was employed to analyze both serum zinc and copperconcentrations. Results: Compared to the control subjects, H.pylori-infected patients had significant decrease in both serum concentrations ofZn and Cu (p=0.000), and BMI was insignificantly increased in patients compared to control (p=0.255).According to recurrent occurrence (once or twice) there wasinsignificant difference between means of serum zinc and copper (p=0.824, 0.869) respectively. Among patient group, Level of serum zinc was insignificant decreased in male compared with female (p=0.409), while serum copper was significantly decrease in male compared with (p=0.013). According to age groups both serum zinc and copper were insignificant deference between groups (p=0.221, p=0.504) respectively. And also there was significant weak positive correlation between zinc and age (p=0.016, r=0.377), and insignificant correlation between copper and age (p=0.148, r=0.233). Serum concentrations of Zn and Cu were significantlydecreased in patients with gastritisHelicobacter pylori.

Manufacturing process accuracy is obtained by proper arrangement of fixture elements known as fixture layout. A N-3-2-1 method is used for sheet metals which requires (N + 3) fixture elements to constrain deformation normal to surface. Genetic Algorithm (GA) is used for fixture layout optimization, but it requires high computational effort due to large number of populations. A new method for fixture layout optimization is proposed by integrating topology optimization into GA. In this method, topology optimization reduces the population for GA. The objective function is to reduce the population for GA and minimize total deformation normal to the plane of workpiece. The proposed approach comprised three stages. In the first stage, the initial number of clamps are determined. In the second stage, the population is reduced for GA and the feasible area of clamps are identified using the topology optimization technique. In the third stage, the number and position of clamps, earlier identi...

The continuous development of industry demands increasing amounts of energy. Hence, there is a quest for obtaining and promoting nonconventional technologies by renewable energy whichfuels the quest for non-conventional technologies used in the field of energy. There are international regulations concerning the management of energy resources in general, which can be applied in managing the renewable energy resources. Romania joined the international efforts in the area of promoting renewable energy resources. The targets assumed (24% of the total energy produced in Romania by 2020 should come from renewable sources) can be achieved if the current regulations and management methods are followed.

INTRODUÇÃO: Os enxertos ósseos são amplamente utilizados em procedimentos reconstrutivos buco-maxilo-faciais. Os campos eletromagnéticos vêm sendo aplicados no reparo de fraturas ósseas e integração de enxertos ósseos (AARON; CIOMBOR, 1993). OBJETIVOS: avaliar a qualidade do reparo de cavidades cirúrgicas com enxertos ósseos sob efeito de um campo magnético permanente, sepultado, in vivo. MATERIAIS E MÉTODOS: utilizou-se uma estrutura metálica constituída de duas arruelas de aço inoxidável, fixadas à estrutura óssea por parafusos de titânio. Neste estudo experimental, com grupos teste e controle, foram selecionados 30 Rattus norvergicus albinus, linhagem Wistar. Os animais foram submetidos à cirurgia acessando-se o fêmur direito para criação de uma cavidade cirúrgica e fixação de um par de dispositivos metálicos, tangenciando as margens dessa cavidade. Em seguida, o osso removido da cavidade cirúrgica foi reimplantado de modo a simular um enxerto ósseo autógeno. Nos gruposteste, as arruelas encontravam-se imantadas, evento que diferiu nos grupos-controle. Os animais foram mortos aos 15, 45 e 60 dias pós-operatórios. As peças foram submetidas à avaliação histológica. RESULTADOS: comparando os grupos-teste e controle durante os períodos experimentais de 15, 45 e 60 dias, houve favorecimento no processo de integração do enxerto ósseo. As formações ósseas, nas proximidades das regiões das arruelas e dos enxertos ósseos autógenos, nos grupos teste aos 45 e 60 dias pós-operatórios, demonstram a ação permanente do campo magnético. CONCLUSÃO: a liga de aço inoxidável imantada, sepultada, in vivo, foi capaz de favorecer o processo de integração do enxerto ósseo. Em todos os tempos experimentais, foi predominante o estímulo da neoformação óssea, no grupo teste quando comparado ao controle.

The Non-steroidal anti-inflammatory drugs [NSAIDs] are acidic either by carboxyl or phenolic groups, which used to date such us mefenamic acid, naproxen, diclofenac, indomethacin, ibuprofen, and aspirin. To minimize the harmful effects of the free group of carboxylic acids found in these NSAIDs on the stomach, 4-Aminoantipyrin (which has analgesic, anti-inflammatory, and antipyretic properties) was selected with six standard non-steroidal anti-inflammatory drugs to change their chemical formulations to obtain a dual suggested drug. The goal of the present research, is to synthesize a new potential non-steroidal anti-inflammatory agents with 4-Aminoantipyrine. These proposed new compounds have been prepared by converting NSAIDs into the corresponding acid chlorides, then treating them directly with 4-amino antipyrin to provide amides (1-6) and thus protecting the stomach from the group of carboxylic acids that may cause stomach ulcers in addition to producing new prodrugs, and identified their physical and spectroscopic FTIR, and NMR properties. Also, our results indicate that compounds containing Antipyrin-NSAIDs moiety have great potential in developing a wide variety of new antibacterial against two Gram (+)ve and three Gram (-)ve bacteria.

ObjectiveTo design a new class of selective neuronal nitric oxide synthase (NOS) inhibitors, and demonstrate that administration in a rabbit model for cerebral palsy (CP) prevents hypoxia‐ischemia–induced deaths and reduces the number of newborn kits exhibiting signs of CP.MethodsWe used a novel computer‐based drug design method called fragment hopping to identify new chemical entities, synthesized them, and conducted in vitro enzyme inhibition studies with the three isozymes of NOS and in vivo experiments to monitor cardiovascular effects on pregnant rabbit dams, NOS activity, and NOx (NO and NO2) concentration in fetal brain, and assess neurobehavioral effects on kits born to saline‐ and compound treated dams.ResultsThe computer‐based design led to the development of powerful and highly selective compounds for inhibition of neuronal NOS over the other isozymes. After maternal administration in a rabbit model of CP, these compounds were found to distribute to fetal brain, to be non...

In the armamentarium of calcium channel blockers appropriately functionalized 3,4-dihydropyrimidin-2(1H)ones have received considerable attention in recent past owing to their structural similarity with 1,4-dihydropyridine based drugs. In this review, we highlight detailed investigations in the calcium channel blocking and other activities of this category of compounds as well as trace their genesis from 1,4-dihydropyridine based drugs.

Background: Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI). Objective and Methods: The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated. Results: The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude o...