Synthesis and evaluation of 1,4-dihydropyridine derivatives with calcium channel blocking activity.

1,4-Dihydropyridines (DHPs) are an important class of L-type calcium channel blockers that are used to treat conditions such as hypertension and angina. Their primary target in the cardiovascular system is the Cav1.2 L-type calcium channel isoform, however, a number of DHPs also block low-voltage-activated T-type calcium channels.

Genetic variations of BRCA1 and BRCA2 genes in dogs with mammary tumours.

Mammary tumours are the most common tumour type in female dogs. The formation of the mammary tumours is multifactorial but the high incidence of tumour disease in certain canine breeds suggests a strong genetic component. BRCA1 and BRCA2 are the most important genes significantly associated with mammary tumours.

Safety risk assessment using analytic hierarchy process (AHP) during planning and budgeting of construction projects.

Introduction: The inherent and unique risks on construction projects quite often present key challenges to contractors. Health and safety risks are among the most significant risks in construction projects since the construction industry is characterized by a relatively high injury and death rate compared to other industries. In construction project management, safety risk assessment is an important step toward identifying potential hazards and evaluating the risks associated with the hazards.

Severe renal tubulopathy in a newborn due to BCS1L gene mutation: effects of different treatment modalities on the clinical course.

Very early onset Toni-Debré-Fanconi Syndrome, a disorder of proximal renal tubules of the kidney which results in the increased urinary excretion of glucose, amino acids, uric acid, phosphate and bicarbonate, could be the manifestation of various inborn errors. Defects of oxidative phosphorylation are a heterogeneous group of disorders with various clinical presentations. Recently, patients with early liver failure, renal tubulopathy and encephalopathy due to the mutations in the BCS1L gene coding for a structural protein in mitochondrial complex III have been described.

Does oxybutynin hydrochloride cause arrhythmia in children with bladder dysfunction?

Aim: Pediatric surgeons frequently encounter children presenting with voiding dysfunction symptoms, including urgency, frequency, and incontinence. Antimuscarinic agents Oxybutynin) are the main drugs used to treat patients with overactive bladder (OAB) syndrome, defined as urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia. Increased QT dispersion is known to be the cause of ventricular arrhythmia in various systemic diseases and leads to increased mortality and morbidity.

Microwave-assisted synthesis and spasmolytic activity of 4-indolylhexahydroquinoline derivatives.

In the present study a microwave-assisted one-pot method was applied for the synthesis of 18 novel condensed 1,4-dihydropyridines carrying the indole moiety. The compounds were achieved by the reaction of appropriate 1,3-cyclohexanedione, substituted indole carboxaldehyde derivative, alkyl acetoacetate and ammonium acetate in methanol, according to a modified Hantzsch reaction. The structure elucidation of the compounds was carried out by spectral methods including X-ray studies.

The relationship between exercise capacity and masked hypertension in sedentary patients with diabetes mellitus.

Aim: Although exaggerated blood pressure responses (EBPR) to exercise have been related to future hypertension and masked hypertension (MHT), the relationship between exercise capacity and MHT remains unclear. A sedentary life style has been related to increased cardiovascular mortality, diabetes mellitus (DM), and hypertension. In this study, we aimed to examine the relationship between exercise capacity and MHT in sedentary patients with DM.

Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells.

Aim: To investigate the effects of hypericin which is obtained from the plant Hypericum perforatum on the expression and the regulation of ADAMTS8 and ADAMTS9 genes in MCF7 breast cancer cells and on the viability of these cells.

Materials And Methods: MCF7 cells were cultured and were separately exposed to 2, 10 and 50 µl/mL of hypericin. After 24 hours, RNA was isolated from these cells and converted to cDNA.

Ethyl 2,7,7-trimethyl-4-(1-methyl-1H-indol-3-yl)-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate.

In the title mol-ecule, C24H28N2O3, the cyclo-hexene ring is in a sofa conformation and the 1,4-dihydro-pyridine ring is in a slight boat conformation. In the indole ring system, the pyrrole and benzene rings form a dihedral angle of 2.63 (7)°.

Ethyl 4-(5-bromo-1H-indol-3-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate.

The title compound, C23H25BrN2O3, crystallizes with two independent mol-ecules in the asymmetric unit (Z' = 2) which differ in the twist of the 5-bromo-1H-indole ring with respect to the plane of the 4-methyl-1,4,5,6,7,8-hexa-hydro-quinoline ring [dihedral angles of 78.55 (9) and 89.70 (8)° in molecules A and B, respectively].

Comprehensive assessment of human pharmacokinetic prediction based on in vivo animal pharmacokinetic data, part 2: clearance.

A comprehensive analysis on the prediction of human clearance based on intravenous pharmacokinetic data from rat, dog, and monkey for approximately 400 compounds was undertaken. This data set has been carefully compiled from literature reports and expanded with some in-house determinations for plasma protein binding and rat clearance. To the authors- knowledge, this is the largest publicly available data set.

Comprehensive assessment of human pharmacokinetic prediction based on in vivo animal pharmacokinetic data, part 1: volume of distribution at steady state.

The authors present a comprehensive analysis on the estimation of volume of distribution at steady state (VD(ss) ) in human based on rat, dog, and monkey data on nearly 400 compounds for which there are also associated human data. This data set, to the authors- knowledge, is the largest publicly available, has been carefully compiled from literature reports, and was expanded with some in-house determinations such as plasma protein binding data. This work offers a good statistical basis for the evaluation of applicable prediction methods, their accuracy, and some methods-dependent diagnostic tools.

Knockdown of Dkk-3 decreases cancer cell migration and invasion independently of the Wnt pathways in oral squamous cell carcinoma‑derived cells.

Oral squamous cell carcinoma (OSCC) is thought to arise as the result of cumulative genetic or epigenetic alterations in cancer-associated genes. We focused on the Dickkopf-3 (Dkk-3) gene as a candidate tumor suppressor in OSCC. Dkk-3 is a potential tumor suppressor, and its downregulation has been reported in various types of malignancies.

The effect of oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine and glutamine on wound healing: a retrospective analysis of diabetic haemodialysis patients.

Background: Diabetes is an important reason for end-stage renal failure and diabetic foot wounds worsen the life qualities of these patients. Protein and amino acid support accelerates the wound healing. The purpose of this retrospective study is to examine the effect of beta-hydroxy-beta-methylbutyrate, arginine and glutamine (Abound) supplementation on the wound healing.

Comparing anterior palatoplasty and modified uvulopalatopharyngoplasty for primary snoring patients: preliminary results.

Objectives: To evaluate and compare the long-term efficacy of modified uvulopalatopharyngoplasty (mUP3) and anterior palatoplasty (AP) techniques for treating snoring in a prospective clinical trial.

Methodology: Patients with total apnea-hypopnea index values < 5/per hour sleep were included in the study. Patients completed the Epworth sleepiness scale (ESS) and snoring visual analogue scale (VAS) before and 24 months after surgery, and a VAS for pain after the operation.

Association of vitamin D receptor gene polymorphisms with colon cancer.

Objective: In this study, we investigated the association of two vitamin D receptor (VDR) polymorphisms BsmI and TaqI with colon cancer in a Caucasian population.

Methods: The VDR gene polymorphisms BsmI and TaqI were detected by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-genotyping assays by using endonucleases BsmI and TaqI, and an agarose gel electrophoresis technique in a series of 43 colon cancer patients and 42 healthy controls.

Results: Allele frequencies and genotype distributions were found to be similar in both cases and controls.

Oxidative ipso substitution of 2,4-difluoro-benzylphthalazines: identification of a rare stable quinone methide and subsequent GSH conjugate.

In vitro metabolite identification and GSH trapping studies in human liver microsomes were conducted to understand the bioactivation potential of compound 1 [2-(6-(4-(4-(2,4-difluorobenzyl)phthalazin-1-yl)piperazin-1-yl)pyridin-3-yl)propan-2-ol], an inhibitor of the Hedgehog pathway. The results revealed the formation of a unique, stable quinone methide metabolite (M1) via ipso substitution of a fluorine atom and subsequent formation of a GSH adduct (M2). The stability of this metabolite arises from extensive resonance-stabilized conjugation of the substituted benzylphthalazine moiety.

Absence of Dickkopf (Dkk)-3 protein expression is correlated with longer disease-free survival and lower incidence of metastasis in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently occurring types of cancer worldwide. We focused on the fact that the aberrant function of Wnt/β-catenin signaling is a frequent event in malignancies. Dickkopf (Dkk)-3 is a major negative regulator of Wnt/β-catenin signaling, which is a known tumor suppressor and is down-regulated in various types of cancer.

Immunohistochemical and morphometric evaluation of neuronal dysfunction in pelviureteral junction obstruction.

Purpose: The pathophysiology of pelviureteral junction obstruction remains unclear. In this study, we attempted to evaluate the neuronal dysfunction using immunohistochemical and morphometric parameters.

Materials And Methods: Using specific antibodies, we studied the neuronal markers and morphometry of specimens from 10 cases of pelviureteral junction obstruction and 10 normal pelviureteral junctions by immunohistochemistry using synaptophysin (synaptic vesicle membrane protein), S-100 (nerve cell fiber marker), protein gene product 9.

A comparative study on the effects of intrathecal morphine added to levobupivacaine for spinal anesthesia.

Objective: In this prospective, randomized, double-blind, controlled study, we investigated the sensory, motor, and analgesic block characteristics oftwo diferent doses of morphine compared with saline when added to 0.5 percent levobupivacaine.

Design: Prospective, randomized, double-blinded, controlled study.

Heparanase and cyclooxygenase-2 gene and protein expressions during progression of oral epithelial dysplasia to carcinoma.

Heparanase and cyclooxygenase-2 (COX-2) are 2 key enzymes that modulate diverse physiological processes during embryonic development and in adult life. Their deregulations have been implicated in the growth and progression of many cancer types. To date, comparatively little is known about the roles of these molecules during oral carcinogenesis.

Role of surrogate markers of atherosclerosis in clinical and subclinical thyroidism.

Background. Data on the relationship between homocysteine, plasminogen activator inhibitor 1, hs-CRP, fibrinogen, and carotid intima media thickness (CA-IMT) is plenty but contradicting and the majority of the studies investigated this issue in only specific thyroidism groups. The aim of this paper was to investigate these relations in patients with subclinical and clinical hypo- and hyperthyroidism.