Metformin use is associated with reduced mortality risk in diabetic patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) and type-2 diabetes (T2D) arguably share pathophysiologic mechanisms, resulting in a more severe phenotype and progression and diabetes is currently considered a risk factor of PD. Besides, research suggests antidiabetic therapies as potential disease-modifying strategies. The main aim was to assess the impact of a metformin-inclusive antidiabetic treatment on patient all-cause mortality. METHODS: A nested case-control prospective study including newly diagnosed PD patients reporting the onset of T2D within ±2 years from the onset of PD (n = 159) and matched (1:5; gender, year of PD onset and age at PD onset) non-diabetic cases (n = 795) followed until death or censoring. Patients on a metformin-inclusive treatment regimen were compared to those receiving other oral anti-diabetics (OADs). RESULTS: Among patients with T2D, 123 were treated with a drug regimen containing metformin (alone [65.0%] or in combination with other drugs [35.0%]) and 36 were prescribed other OADs. During a median PD duration of 96 months [IQR, 60-144], 171 patients died. Diabetes was not associated with reduced survival: fully-adjusted HR = 1.19 [95%CI, 0.81-1.76] (P = 0.37). After stratifying for T2D treatment, a metformin-inclusive regimen was not associated with increased risk of death (HR = 1.06 [95%CI, 0.61-1.84]; P = 0.83), while patients receiving other OADs had reduced survival (HR = 1.83 [95%CI, 1.01-3.32]; P = 0.034). CONCLUSIONS: Metformin use was not associated with increased risk of death in diabetic patients with PD reporting concomitant onset of the two diseases. Metformin appears to be a promising disease-modifying therapy given also the preclinical background, low cost and satisfactory safety and tolerability. Further studies are warranted to investigate its impact on disease progression.

Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review.

Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic.

Anti-diabetics and the Prevention of Dementia: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic condition caused by reduced insulin secretion and increased insulin resistance. Due to insulin not operating at optimal conditions, blood glucose rises and remains high, thus disturbing metabolic hemostasis. Many complications can arise from T2DM, such as coronary vascular disease, kidney damage, eye damage, and, quite significantly, dementia. It is theorized that dementia from T2DM stems from the fact that the brain is susceptible to hyperglycemic conditions, which are promoted by the increase in insulin resistance of target cells in the central nervous system. This directly affects cognitive processes and memory, which correlates to decreased temporal and front lobes volume. The risk of diabetic complications can be minimized with therapeutic interventions such as oral-antidiabetic (OAD) agents and insulin. Several OADs are on the market, but the first-line agent is metformin, a biguanide that decreases glucose production and increases insulin sensitivity. This paper aims to determine if currently prescribed OADs can help slow cognitive decline and reduce the risk and incidence of dementia as a complication of T2DM. Studies found that, for the most part, all OADs except sulfonylureas (SU) significantly slowed the decline of cognitive function and reduced the risk and incidence of dementia. SU's were shown to increase the risk of dementia in most studies. Of all the OADs, thiazolidinediones may be the most beneficial drug class for reducing the risk of dementia in T2DM patients. Future research should focus on whether early intervention with specific classes of OADs can not only improve glycemic control, leading to decreased hyperglycemia but also prevent the build-up of damaged brain tissue and help to reduce the risk and incidence of dementia in patients with T2DM.

In-silico Assessment of Polyherbal Oils as Anti-diabetic Therapeutics.

BACKGROUND: Diabetes mellitus (DM) is characterized by elevated blood glucose levels either due to insufficient insulin production, defective insulin action, or both. It affects nearly 537 million individuals worldwide. Pharmacological treatment involves the use of oral antidiabetic agents as mono or combination therapy that effectively aids in controlling hyperglycemia. Despite providing therapeutic benefits, these medications limit their use owing to adverse side effects. Certain natural products, including essential oils, have promising anti-diabetic properties. OBJECTIVE: The present study explores the effectiveness of two polyherbal oils and their compound towards the treatment of DM based on an In-silico approach to drug investigations. METHODS: Compounds present in the polyherbal oil formulation were identified using GCMS/MS analysis. Selected compounds undergo molecular docking with the receptor, and proteins play an important role in DM. The potential compounds showing higher interactions than the known inhibitors or inducers were evaluated using molecular dynamic simulations RMSD values. RESULTS: The compounds identified through GC-MS analysis possess anti-diabetic and antiinflammatory properties. With the aid of in silico prediction methods, compounds such as geraniol, cinnamaldehyde, anethole, caryophyllene, terpinyl acetate, cymene, linalool, menthol, Phenol,2-methoxy-3-(2-propenyl), and 2,6- octadienal,3,7-dimethyl were identified as strong binders of GLUT4 and insulin receptor proteins. Geraniol and Phenol,2-methoxy-3-(2-propenyl) interaction with GLUT4 were of particular importance owing to their conformational stability. CONCLUSION: Our data suggest an agonistic effect of compounds on target proteins aiding in enhanced insulin activity and could serve as a potential anti-diabetic agent.

Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials.

Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aß production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.

Diabetes and seeds: New horizon to promote human nutrition and anti-diabetics compounds in grains by germination.

Type 2 diabetes (T2D) is a complex and heterogeneous chronic metabolic disorder disease that is associated with high blood sugar. Because of the side effects of synthetic drugs on T2D patients and their economic burden, interest in plant-derived functional foods like grains with biological activities has developed. Based on scientific reports, whole grains are rich sources of energy, nutrients, and bioactive compounds and are assumed to have beneficial health effects on glucose enzymes regulation or hyperglycemia. Nowadays, different methods have been applied to enhance whole seed healthful properties and anti-diabetic compounds, and germination is one of them. Germination (sprouting) is a cost-effective method for boosting the activity of endogenous seed enzymes and modifying the structure of macromolecules. Some of these macromolecules like bioactive peptides, polyphenols, dietary fiber, and vitamins are related to diabetes management. Determining the best germination condition can help to promote these anti-diabetics properties of compounds. This study presents relevant information about diabetes, the effect of seed germination on releasing bioactive compounds, and optimizing environmental germination conditions to improve the anti-diabetic compounds in seeds for reaching functional food.

Anti-diabetics and antimicrobials: Harmony of mutual interplay.

Diabetes is one of the four major non-communicable diseases, and appointed by the world health organization as the seventh leading cause of death worldwide. The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes. The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes, assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation. On a parallel basis, microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment, all of which can be reversed by antimicrobial treatment. Standing at the crossroads between diabetes, immunity and infection, we aim in this review at projecting the interplay between immunity and diabetes, shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents. Furthermore, we focused on the anti-diabetic drugs that can confer antimicrobial or anti-virulence activities.

The Effect of Type-2 Diabetes on Cognitive Status and the Role of Anti-diabetes Medications.

Type-2 diabetes mellitus prevalence is constantly increasing; this is explained by the increase of its risk factors and the amelioration of its management. Therefore, people are living longer with diabetes mellitus, which, in turn, has revealed new complications of the disease. Dementia is represented mainly by Alzheimer's disease and is an interesting topic of study. Accordingly, statistics have shown that dementia incidence is doubled in diabetic patients. The establishment of a relation between type-2 diabetes mellitus was studied on several levels in both humans and animal subjects. First, insulin receptors were found in the brain, especially the hippocampus, and insulin transport to the brain is mainly accomplished through the blood-brain barrier. Secondly, several studies showed that insulin affects multiple neurotransmitters in favor of promoting memory and cognition status. Thirdly, multiple pathological studies showed that insulin and Alzheimer's disease share many common lesions in the brain, such as beta-amyloid plaques, amylin-Aß plaques, hyper-phosphorylated tau protein, and brain atrophy, especially in the hippocampus. After recognizing the positive effect of insulin on cognitive status, and the harmful effect of insulin resistance on cognitive status, multiple studies were focused on the role of anti-diabetes medications in fighting dementia. Consequently, these studies showed a positive impact of oral anti-diabetes medication, as well as insulin in limiting the progression of dementia and promoting cognitive status. Moreover, their effects were also noticed on limiting the pathological lesions of Alzheimer's disease. Accordingly, we can consider type-2 diabetes mellitus as a risk factor for dementia and Alzheimer's disease. Therefore, this can be used on the pharmaceutical level by the promising implication of antidiabetics as a treatment of dementia and Alzheimer's disease or at least to limit its progression. However, multiple clinical studies should be dedicated to proving the true benefits of anti-diabetes medications in treating dementia before they can be used in reality.

GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach.

The current study aimed to explore the crude oils obtained from the n-hexane fraction of Scutellaria edelbergii and further analyzed, for the first time, for their chemical composition, in vitro antibacterial, antifungal, antioxidant, antidiabetic, and in vivo anti-inflammatory, and analgesic activities. For the phytochemical composition, the oils proceeded to gas chromatography-mass spectrometry (GC-MS) analysis and from the resultant chromatogram, 42 bioactive constituents were identified. Among them, the major components were linoleic acid ethyl ester (19.67%) followed by ethyl oleate (18.45%), linolenic acid methyl ester (11.67%), and palmitic acid ethyl ester (11.01%). Tetrazolium 96-well plate MTT assay and agar-well diffusion methods were used to evaluate the isolated oil for its minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC), half-maximal inhibitory concentrations (IC50), and zone of inhibitions that could determine the potential antimicrobial efficacy's. Substantial antibacterial activities were observed against the clinical isolates comprising of three Gram-negative bacteria, viz., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and one Gram-positive bacterial strain, Enterococcus faecalis. The oils were also effective against Candida albicans and Fusarium oxysporum when evaluated for their antifungal potential. Moreover, significant antioxidant potential with IC50 values of 136.4 and 161.5 µg/mL for extracted oil was evaluated through DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays compared with standard ascorbic acid where the IC50 values were 44.49 and 67.78 µg/mL, respectively, against the tested free radicals. The oils was also potent, inhibiting the α-glucosidase (IC50 5.45 ± 0.42 µg/mL) enzyme compared to the standard. Anti-glucosidase potential was visualized through molecular docking simulations where ten compounds of the oil were found to be the leading inhibitors of the selected enzyme based on interactions, binding energy, and binding affinity. The oil was found to be an effective anti-inflammatory (61%) agent compared with diclofenac sodium (70.92%) via the carrageenan-induced assay. An appreciable (48.28%) analgesic activity in correlation with the standard aspirin was observed through the acetic acid-induced writhing bioassay. The oil from the n-hexane fraction of S. edelbergii contained valuable bioactive constituents that can act as in vitro biological and in vivo pharmacological agents. However, further studies are needed to uncover individual responsible compounds of the observed biological potentials which would be helpful in devising novel drugs.

Fixed Drug Eruption Secondary to Four Anti-diabetic Medications: An Unusual Case of Polysensitivity.

We report a case of fixed drug eruption in a 58-year-old lady treated for diabetes with four pharmacologically different anti-diabetic agents that were used at separate times of therapy. Skin manifestations, including erythema, blisters, and ulcers, developed over the right leg each time after the initiation of metformin, gliclazide, vildagliptin, and empagliflozin; and disappeared following the discontinuation of the drugs. Magnesium stearate was the common excipient identified in the four agents. This is an extremely rare case of fixed drug eruption caused by structurally dissimilar drugs.

Use of non-insulin antidiabetic drugs in children and young adults - A Scandinavian drug utilization study from 2010-2019.

Knowledge on utilization patterns of non-insulin antidiabetic drugs in childhood and youth is limited. Therefore, we conducted a population-based drug utilization study using publicly available aggregate data on use of non-insulin antidiabetics from 2010 to 2019 in Scandinavia (Denmark, Norway and Sweden) in individuals aged up to 24 years. For each non-insulin antidiabetic drug, we calculated the annual prevalence proportion of users, overall and for specific age groups. From 2010 to 2019, the prevalence of non-insulin antidiabetic users in Scandinavia increased 37% from 0.43 to 0.59/1000 individuals. The prevalence proportions were highest among female adolescents and young adults, but the largest relative increase in use was seen among 10-14-year-olds (78%). Metformin was by far the most widely used non-insulin antidiabetic drug with a prevalence proportion of 0.51/1000 in 2019, followed by glucagon-like peptide-1 (GLP-1) analogues, which, however, showed an eight-fold relative increase during the study period.

Investigation into the role of anti-diabetic agents in cachexia associated with metastatic cancer.

Cancer cachexia (CC) is a syndrome associated with cancer, and the global burden is increasing rapidly. Alteration in carbohydrate, lipid and protein metabolism along with systemic inflammation are characteristics of CC. Until now the available treatment for CC is limited to controlling inflammation and nutrition. Anti-diabetics are widely used agents to treat diabetics, this agent's act by regulating the carbohydrate metabolism, also they are known to have beneficial effects in maintaining protein and lipid balance. Role of anti-diabetics in cancer is being evaluated continuously and biguanides, dipeptidyl peptidase 4 (DPP4) inhibitors and Sodium glucose co-transporter 2 (SGLT2) inhibitors have proven anti-cancer potential. In this study, metastatic B16-F1 cell line induced cancer cachexia model used to evaluate potential of biguanides (metformin), DPP-4 inhibitors (teneligliptin and vildagliptin) and SGLT2 inhibitors (empagliflozin and dapagliflozin) in cancer cachexia. Our results suggest that anti-diabetic agents have potential to decrease rate of proliferation of tumor, restrict body mass markers, decrease inflammation, regulate carbohydrate mechanism and induce skeletal muscle hypertrophy. These findings may be helpful in management of cancer cachexia and increase the quality of life and survival chances of cancer cachexia patient.

An overview on synthetic and pharmaceutical prospective of pyrido[2,3-d]pyrimidines scaffold.

Pyrido[2,3-d]pyrimidine, a fused hetero-bicyclic nucleus containing pyridine and pyrimidine rings has attained the momentary attention in the sphere of multicomponent synthetic protocol and medicinal chemist. Pyrido[2,3-d]pyrimidine derived drugs have manifested diverse pharmacological activities, particularly, anti-inflammatory, cytotoxic, antimicrobial, phosphodiesterase inhibitors and cytokine inhibitors etc. The present review illustrates various modern synthetic strategies adopted, the structure-activity relationship (SAR) aspects and discloses the extensive crucial biological properties (anticancer, anti-infectious, anti-diabetics and CNS agents) of pyrido[2,3-d]pyrimidines.

Oral anti-diabetic drugs as endocrine disruptors in vitro - No evidence for additive effects in binary mixtures.

Diabetes is one of the World's most concerning health problems and millions of patients are using anti-diabetic drugs (ADDs) in order to control blood glucose. The in vitro H295R steroidogenesis assay was implemented to investigate endocrine effects of three ADDs, metformin (MET), glimepiride (GLIM), sitagliptin (SIT) and the cholesterol-lowering drug simvastatin (SIM) individually and in three binary mixtures. Steroid hormones were analyzed using LC-MS/MS. Mixture effects were assessed by applying the Concentration Addition (CA) model. All tested drugs and binary mixtures interrupted the H295R steroidogenesis with different potency. The effects of MET:GLIM on the steroidogenesis were overall similar to the steroidogenic profile of GLIM, however effects were less pronounced. The binary mixture of MET:SIT showed overall minor effects on steroid production and only at very high concentrations. The SIM:SIT mixture showed inhibition downstream from cholesterol, which was attributed to the effects of SIM. The CA model partly predicted the effect of MET:SIT on some steroids but significantly overestimated the effects of MET:GLIM and SIM:SIT. Thus, the applicability of the CA model was limited and cocktail effects appeared to be intermediate responses of individual drugs, rather than additive. The complexity of dynamic pathways such as steroidogenesis appears to significantly reduce the use of the CA model. In conclusion, more dynamic models are needed to predict mixture effects in complex systems.

Anti-Microbial, Anti-Oxidant, and α-Amylase Inhibitory Activity of Traditionally-Used Medicinal Herbs: A Comparative Analyses of Pharmacology, and Phytoconstituents of Regional Halophytic Plants' Diaspora.

Halophytes are the category of plants growing under harsh conditions of super-salinity, and are wide-spread in the coastal Mediterranean climatic conditions and desert oasis. They are adept at surviving through maintaining excessive production of enzymatic, and non-enzymatic secondary metabolites, especially phenolics and flavonoids that primarily work as anti-oxidants and phytoalexins. Five major halophyte species growing in the kingdom's Qassim's high-salted desert regions were investigated for confirming their traditionally used biological activity of sugar-control and anti-infectious properties. In this context, the comparative presence of phenolics, and flavonoids together with anti-microbial, anti-oxidants, and the anti-diabetic potentials of the plants' extracts were investigated through the α-amylase inhibition method. The highest concentrations of phenolics and flavonoids were detected in Salsola imbricata (360 mg/g of the extract as Gallic-Acid-Equivalents/GAE, and 70.5 mg/g of the extract as Rutin-Equivalents/RE). In contrast, the lowest concentrations of phenolics and flavonoids were detected in Salsola cyclophylla (126.6 mg/g GAE, and 20.5 mg/g RE). The halophytes were found rich in trace elements, a factor for water-retention in high-salinity plants, wherein iron and zinc elements were found comparatively in higher concentrations in Aeluropus lagopoides (4113 µg/kg, and 40.1 µg/kg, respectively), while the copper was detected in higher concentration (11.1 µg/kg) in S. imbricata, analyzed through Inductively Coupled Plasma Optical Emission Spectrometric (ICP-OES) analysis. The anti-oxidant potentials and α-amylase enzyme inhibition-based anti-diabetic activity of S. imbricata was significantly higher than the other halophytes under study, wherein S. cyclophylla exhibited the lowest level of α-amylase inhibition. The maximum DPPH radicals' (52.47 mg/mL), and α-amylase inhibitions (IC50 22.98 µg/mL) were detected in A.lagopoides. The anti-microbial activity against the Methicillin-Resistant Staphylococcus aureus was strongly exhibited by Zygophyllum simplex (33 mm Inhibition Zone-Diameter, 50 µg/mL Minimum-Inhibitory-Concentration), while Escherichia coli, Enterococcus faecalis, and Candida albicans growths were moderately inhibited by Tamarix aphylla. The current findings exhibited significant differences among the locally distributed halophytic plants species with regards to their bioactivity levels, anti-oxidant potentials, and the presence of trace elements. The ongoing data corroborated the plants' traditional uses in infections and diabetic conditions. The enhanced local distribution of the plants' diaspora and higher density of occurrence of these plants species in this region, in comparison to their normal climatic condition's counterparts, seemed to be affected by humans' use of the species as part of the traditional and alternative medicine over a period of long time.

Effect of X-Ray Irradiation on Some Analgesics, Anti-Diabetics, PPI'S, Anti-Hypertensives, Heart Failure Drugs in Tablet and Capsule Forms.

X-ray is an ionizing-radiation and it has been used in many processes due to the developing technology. For security purposes, X-ray instruments are been using at the entrance of the airports, shopping centers, etc. In this study, potential effects of X-ray were investigated on five different types of drugs: analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), proton pump inhibitors (lansoprazole, pantoprazole sodium sesquihydrate), anti-diabetics (metformin HCl, pioglitazone), heart failure drugs (verapamil HCl, spironolactone) and anti-hypertensives (losartan, clopidogrel hydrogen sulphate) by several different methods. In our previous study these drugs were analyzed by ESR before and after X-ray irradiation (0,24; 1,2; 58 mGy). According to the ESR results, acetylsalicylic acid tablets were affected after 58 mGy irradiation due to coated polymer (HPMC). In conclusion, these drugs were investigated before and after 0,24; 1,2 and 58 mGy X-ray irradiation by UV-spectrophotometry, dissolution test, SEM, FT-IR, DSC/TGA in this article. As a result of this study, X-ray did not cause a significant effect on drugs generally. Only a few significant differences were detected by different studies (for metformin HCl by DSC/TGA, for acetylsalicylic acid by dissolution test, and for acetaminophen and acetylsalicylic acid by UV spectrophotometry were detected significantly difference before and after irradiation).

Prophylactic and therapeutic roles of oleanolic acid and its derivatives in several diseases.

Oleanolic acid (OA) and its derivatives are widely found in diverse plants and are naturally effective pentacyclic triterpenoid compounds with broad prophylactic and therapeutic roles in various diseases such as ulcerative colitis, multiple sclerosis, metabolic disorders, diabetes, hepatitis and different cancers. This review assembles and presents the latest in vivo reports on the impacts of OA and OA derivatives from various plant sources and the biological mechanisms of OA activities. Thus, this review presents sufficient data proposing that OA and its derivatives are potential alternative and complementary therapies for the treatment and management of several diseases.

ESR INVESTIGATIONS of X-RAY EXPOSED DRUGS.

X-ray is used in several areas for analysis, imaging, sterilisation and security. X-ray machines are increasingly used in the entrance of the airports, shopping centres, etc. for security purposes. Therefore, human beings and belongings are frequently exposed to X-ray by transiting these checkpoints at various sites such as airports, shopping centres etc. This study aims is to investigate the X-rays potential effects (arising from security machines) on different groups of medicines which are analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), anti-diabetics (metformin HCl, pioglitazone), PPI's (lansoprazole, pantoprazole sesquihydrate), anti-hypertensives (losartan, clopidogrel hydrogen sulphate), heart failure medicines (verapamil HCl, spironolactone) used frequently and daily, by using ESR analysis. Coated acetylsalicylic acid tablets showed different intensities of ESR signals after 58 mGy irradiation. It thought to be the result of the coating polymer (Hydroxypropylmethylcellulose (HPMC)). According to the ESR results which were obtained for 0,24-58 mGy irradiated drugs- 1 hour after irradiation (refrigerated during this period) X-ray did not affect those medicines except the acetylsalicylic acid tablets significantly. The meaningful differences were only obtained between the non-irradiated, and 58 mGy irradiated acetylsalicylic acid tablets. Therefore, it can be concluded that X-ray exposed medicines, except coated acetylsalicylic acid tablets (after 58 mGy irradiation), can be used safely for the irradiation levels used in this study (0.24 mGy-0.58 mGy). In addition those data, ESR analyses were followed by other analysis such as FT-IR, DSC/TGA, dissolution, SEM, etc., and they are planned to be published soon.

Antidiabetic and antiosteoporotic pharmacotherapies for prevention and treatment of type 2 diabetes-induced bone disease: protocol for two network meta-analyses.

INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are at risk for a variety of severe debilitating effects. One of the most serious complications experienced by patients with T2DM are skeletal diseases caused by changes in the bone microenvironment. As a result, patients with T2DM are at risk for higher prevalence of fragility fractures. There are a variety of treatments available for counteracting this effect. Some antidiabetic medications, such as metformin, have been shown to have a positive effect on bone health without the addition of additional drugs into patients' treatment plans. Chinese randomised controlled trial (RCT) studies have also proposed antiosteoporotic pharmacotherapies as a viable alternative treatment strategy. Previous network meta-analyses (NMAs) and meta-analyses regarding this topic did not include all available RCT trials, or only performed pairwise comparisons. We present a protocol for a two-part NMA that incorporates all available RCT data to provide the most comprehensive ranking of antidiabetics (part I) and antiosteoporotic (part II) pharmacotherapies in terms of their ability to decrease fracture incidences, increase bone mineral density (BMD) and improve indications of bone turnover markers (BTMs) in adult patients with T2DM. METHODS AND ANALYSIS: We will search Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and Chinese literature sources (China National Knowledge Infrastructure, Chongqing VIP Information, Wanfang Data, Wanfang Med Online) for RCTs, which fit our criteria. We will include adult patients with T2DM who have taken antidiabetics (part I) or antiosteoporotic (part II) therapies with relevant outcome measures in our study. We will perform title/abstract and full-text screening as well as data extraction in duplicate. Risk of bias will be evaluated in duplicate for each study, and the quality of evidence will be examined using Confidence in Network Meta-Analysis in accordance to the Grading of Recommendations Assessment, Development and Evaluation framework. We will use R and gemtc to perform the NMA. We will report changes in BMD and BTMs in either weighted or standardised mean difference, and we will report fracture incidences as ORs. We will use the Surface Under the Cumulative Ranking Curve scores to provide numerical estimates of the rankings of interventions. ETHICS AND DISSEMINATION: The study will not require ethics approval. The findings of the two-part NMA will be disseminated in peer-reviewed journals and presented at conferences. We aim to produce the most comprehensive quantitative analysis regarding the management of T2DM bone disease. Our analysis should be able to provide physicians and patients with up-to-date recommendations for antidiabetic medications and antiosteoporotic pharmacotherapies for maintaining bone health in patients with T2DM. PROSPERO REGISTRATION NUMBER: CRD42019139320.