Serum markers of bone fragility in type-2 diabetes mellitus

Patients with type-2 diabetes mellitus (T2DM) have normal or increased bone mineral density (BMD) but despite that, they are characterized by an increased hip and vertebral fracture risk that involves the alteration of bone quality and not the reduction in bone mass. BMD is utilized for the diagnosis and evaluation of osteoporosis, but BMD itself cannot provide an accurate diagnosis of the individuals at increased risk of fracture and, therefore, studies have focused on identifying other risk factors that are partially or fully independent of BMD. The fracture risk score tool-FRAX® models provide information about a 10-year probability of osteoporotic fractures, but do not include risk factors specific to illness such as diabetes duration, diabetes drug therapy, glycemic control, or the presence of micro-vascular complications. Multiple markers have been investigated to provide information on the risk of fractures in patients with T2DM such as: advanced glycation end products (AGEs), insulin-like growth factor-I (IGF-I), osteocalcin (OC), adiponectin, and sclerostin, but epidemiological studies did not provide homogeneous information regarding the link between these markers and bone fragility in T2DM subjects. Markers that increase the accuracy of fracture risk estimation in patients with T2DM need to be identified and employed in current medical practice

Serum markers of bone fragility in type-2 diabetes mellitus

Patients with type-2 diabetes mellitus (T2DM) have normal or increased bone mineral density (BMD) but despite that, they are characterized by an increased hip and vertebral fracture risk that involves the alteration of bone quality and not the reduction in bone mass. BMD is utilized for the diagnosis and evaluation of osteoporosis, but BMD itself cannot provide an accurate diagnosis of the individuals at increased risk of fracture and, therefore, studies have focused on identifying other risk factors that are partially or fully independent of BMD. The fracture risk score tool-FRAX® models provide information about a 10-year probability of osteoporotic fractures, but do not include risk factors specific to illness such as diabetes duration, diabetes drug therapy, glycemic control, or the presence of micro-vascular complications. Multiple markers have been investigated to provide information on the risk of fractures in patients with T2DM such as: advanced glycation end products (AGEs), insulin-like growth factor-I (IGF-I), osteocalcin (OC), adiponectin, and sclerostin, but epidemiological studies did not provide homogeneous information regarding the link between these markers and bone fragility in T2DM subjects. Markers that increase the accuracy of fracture risk estimation in patients with T2DM need to be identified and employed in current medical practice

Determination of pyrrolizidine alkaloids in dietary sources using a spectrophotometric method

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds found in the composition of more than 6000 plants. People can be exposed to PAs by consuming phytotherapeutic products, food from crops contaminated with seeds of some species with high content of PAs, and/ or contaminated animal products like bee products. For this reason we developed and validated a method for quantitative determination of PAs, from the most frequently contaminated food sources, honey and flour. Colorimetric Ehrlich reagent method was used with standard addition (1mg/kg senecionine). The extraction solvent was methanol 50% acidified with citric acid to pH 2-3, as this solvent can be used for alkaloids and N-oxides. We found that, in extracting the alkaloid only once from the dietary sources, the percent of recovery is low (52.5% for honey, and 45.75% for flour). Using successive extractions, three times with the same solvent, the senecionine retrieval percentage increased to 86.0% for honey and 76.0% for flour. The method was validated using the following parameters: selectivity, linearity (0,25- 20 mg/ mL senecionine), accuracy (average recovery 93.5 - 107.93%) and precision (RSD 3,26-4.55%.). The calculated limit of quantification (0.174 mg/ mL) makes this method applicable for determining Pas occurring at toxic levels for consumers

Serum markers of bone fragility in type-2 diabetes mellitus

Patients with type-2 diabetes mellitus (T2DM) have normal or increased bone mineral density (BMD) but despite that, they are characterized by an increased hip and vertebral fracture risk that involves the alteration of bone quality and not the reduction in bone mass. BMD is utilized for the diagnosis and evaluation of osteoporosis, but BMD itself cannot provide an accurate diagnosis of the individuals at increased risk of fracture and, therefore, studies have focused on identifying other risk factors that are partially or fully independent of BMD. The fracture risk score tool-FRAX® models provide information about a 10-year probability of osteoporotic fractures, but do not include risk factors specific to illness such as diabetes duration, diabetes drug therapy, glycemic control, or the presence of micro-vascular complications. Multiple markers have been investigated to provide information on the risk of fractures in patients with T2DM such as: advanced glycation end products (AGEs), insulin-like growth factor-I (IGF-I), osteocalcin (OC), adiponectin, and sclerostin, but epidemiological studies did not provide homogeneous information regarding the link between these markers and bone fragility in T2DM subjects. Markers that increase the accuracy of fracture risk estimation in patients with T2DM need to be identified and employed in current medical practice

Synthesis and Pharmacological Research Regarding New Compounds with Quinazolin-4-One Structure

The quinazoline scaffold is found in the chemical structure of many marketed drugs used in CNS disorders as antidepressants, anxiolytics, or hypnotics. Also, the carbamate ester derivatives have different certain therapeutic actions, such as hypnotic or parasympathomimetic ones. We have obtained new 4(3H)-quinazolinones by bringing together in the same structure the quinazoline nucleus and carbamate ester group. The compounds named Q1–Q5 were characterized by measuring the melting points, by determining the infrared and NMR spectra, and by elemental analysis. The pharmacological tests evidenced that the compounds have a very low acute toxicity, lethal doses being >2000 mg/kg bw. The compounds had different actions observed in forced swimming test (FST), tail suspension test (TST), or elevated plus maze (EPM), probably influenced by the presence of different radicals on the nucleus. Thus, Q1 with a nitro group in structure manifested the highest antidepressant effect, showing a reduction of immobilization time in FST and TST. On the other hand, Q3 and Q5, with two groups methoxy, respective ethoxy, had a slight anxiolytic effect, highlighted by an increase of the time spent in open arms and a decrease of the time spent in closed arms of EPM

Determination of pyrrolizidine alkaloids in dietary sources using a spectrophotometric method

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds found in the composition of more than 6000 plants. People can be exposed to PAs by consuming phytotherapeutic products, food from crops contaminated with seeds of some species with high content of PAs, and/ or contaminated animal products like bee products. For this reason we developed and validated a method for quantitative determination of PAs, from the most frequently contaminated food sources, honey and flour. Colorimetric Ehrlich reagent method was used with standard addition (1mg/kg senecionine). The extraction solvent was methanol 50% acidified with citric acid to pH 2-3, as this solvent can be used for alkaloids and N-oxides. We found that, in extracting the alkaloid only once from the dietary sources, the percent of recovery is low (52.5% for honey, and 45.75% for flour). Using successive extractions, three times with the same solvent, the senecionine retrieval percentage increased to 86.0% for honey and 76.0% for flour. The method was validated using the following parameters: selectivity, linearity (0,25- 20 mg/ mL senecionine), accuracy (average recovery 93.5 - 107.93%) and precision (RSD 3,26-4.55%.). The calculated limit of quantification (0.174 mg/ mL) makes this method applicable for determining Pas occurring at toxic levels for consumers

The Influence of Sildenafil–Metformin Combination on Hyperalgesia and Biochemical Markers in Diabetic Neuropathy in Mice

Background and objectives: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing diabetic neuropathy (DN)-associated pain are limited and have several side effects. The purpose of the study was to evaluate the antihyperalgesic action of different sildenafil (phosphodiesterase-5 inhibitor) and metformin (antihyperglycemic agent) combinations in alloxan-induced DN. Methods: The study included 100 diabetic mice and 20 non-diabetic mice that were subjected to hot and cold stimulus tests. Furthermore, we determined the influence of this combination on TNF-α, IL-6 and nitrites levels in brain and liver tissues. Results: In both the hot-plate and tail withdrawal test, all sildenafil–metformin combinations administered in our study showed a significant increase in pain reaction latencies when compared to the diabetic control group. Furthermore, all combinations decreased blood glucose levels due to the hypoglycemic effect of metformin. Additionally, changes in nitrite levels and pro-inflammatory cytokines (TNF-α and IL-6) were observed after 14 days of treatment with different sildenafil–metformin combinations. Conclusions: The combination of these two substances increased the pain reaction latency of diabetic animals in a dose-dependent manner. Moreover, all sildenafil–metformin combinations significantly reduced the concentration of nitrites in the brain and liver, which are final products formed under the action of iNOS

Wound Healing and Anti-Inflammatory Effects of a Newly Developed Ointment Containing Jujube Leaves Extract

Ziziphus jujuba Mill. (jujube) is a well-known medicinal plant with pronounced wound healing properties. The present study aimed to establish the chemical composition of the lyophilized ethanolic extract from Romanian Ziziphus jujuba leaves and to evaluate the healing and anti-inflammatory properties of a newly developed lipophilic ointment containing 10% dried jujube leaves extract. The ultra-High-Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry method was used, and 47 compounds were detected, among them the novel epicatechin and caffeic acid. The extract contains significant amounts of rutin (29.836 mg/g), quercetin (15.180 mg/g) and chlorogenic acid (350.96 µg/g). The lipophilic ointment has a slightly tolerable pH, between 5.41–5.42, and proved to be non-toxic in acute dermal irritation tests on New Zealand albino rabbits and after repeated administration on Wistar rats. The ointment also has a healing activity comparable to Cicatrizin (a pharmaceutical marketed product) on Wistar rats and a moderate anti-inflammatory action compared to the control group, but statistically insignificant compared to indomethacin in the rat-induced inflammation test by intraplantar administration of kaolin. The healing and anti-inflammatory properties of the tested ointment are due to phenolic acids and flavonoids content, less because of minor components as apocynin, scopoletin, and isofraxidin