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European Endocrinology Apr 2017Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable... (Review)
Review
Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable prices remains a global issue. The world is experiencing an exponential rise in the prevalence of diabetes presenting an urgent need to establish effective diabetes therapy in countries burdened by inadequate health care budgets, malnutrition and infectious diseases. Recombinant human insulin has replaced animal insulins and animal-based semisynthetic human insulin thereby available in sufficient quantities and at affordable prices able to provide global access to insulin therapy. In many patients, analog insulins can offer additional clinical benefit, although at a considerably higher price thus severely restricting availability in low income countries. The approval process for recombinant human insulins (i.e. biosimilars) and analogue insulins is highly variable in the developing countries in contrast to Europe and in North America, where it is well established within a strict regulatory framework. This review aims to discuss the future access to human insulin therapy in a global context with an ever increasing burden of diabetes and significant economic implications.
PubMed: 29632602
DOI: 10.17925/EE.2017.13.01.21 -
Brazilian Journal of Otorhinolaryngology 2019Tinnitus is a subjective auditory symptom usually associated with a sound, even in the absence of external sound sources. Its diagnosis is complex, and some of the forms...
INTRODUCTION
Tinnitus is a subjective auditory symptom usually associated with a sound, even in the absence of external sound sources. Its diagnosis is complex, and some of the forms of measurement alone or in combination, include self-assessment questionnaires, such as the tinnitus handicap inventory, the visual analog scale and/or pitch and loudness matching.
OBJECTIVE
To analyze the correlation among three tinnitus measurement methods: tinnitus handicap inventory, visual analog scale and pitch and loudness matching.
METHODS
The study consisted of 148 patients complaining of chronic tinnitus. An otorhinolaryngological evaluation, anamnesis directed to tinnitus, audiometry (pure tone and speech), imitanciometry, tinnitus handicap inventory, visual analog scale, and pitch and loudness matching were performed. The study was registered in the Ethics Committee of the Institution with no. 0129/12.
RESULTS
Regarding the frequency of tinnitus handicap inventory responses, a higher occurrence of the mild degree was observed. An average of 6 points was observed on the visual analog scale. The mean loudness matching in the right ear was 20dBNS, and in the left ear was 17dBNS. As for the type of stimulus, the most found was continuous pure tone. The frequency of the pitch sensation was 6000Hz in the largest number of cases. Regarding the measures of tinnitus handicap inventory and the visual analogical scale, a significant correlation was observed, and as one value increases the other also increases. Pitch and loudness matching and the visual analogical scale results are also significant.
CONCLUSION
There was a significant correlation between the values measured by the tinnitus handicap inventory, visual analogical scale (annoyance) and loudness matching in the evaluation of tinnitus. The selection of any one of the three evaluative methods for tinnitus investigation provides different dimensions of the tinnitus and complements the others.
Topics: Adolescent; Adult; Audiometry, Pure-Tone; Female; Humans; Male; Middle Aged; Sound Localization; Surveys and Questionnaires; Tinnitus; Visual Analog Scale; Young Adult
PubMed: 29983341
DOI: 10.1016/j.bjorl.2018.05.006 -
Molecules (Basel, Switzerland) Apr 2020Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including... (Review)
Review
Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including gemcitabine and cytarabine, are the go-to option in first-line treatments. However, these materials do have limitations and the development of next generation compounds remains a topic of significant interest and necessity. Herein, we discuss recent advances in the chemical synthesis and biological evaluation of nucleoside analogues as potential anticancer agents. Focus is paid to 4'-heteroatom substitution of the furanose oxygen, 2'-, 3'-, 4'- and 5'-position ring modifications and the development of new prodrug strategies for these materials.
Topics: Adenosine; Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Design; Drug Screening Assays, Antitumor; Furans; Humans; K562 Cells; Mice; Molecular Structure; Nucleosides; Oxygen; Prodrugs; Purine Nucleosides; Pyrimidinones; Thionucleosides; Vitamin E
PubMed: 32354007
DOI: 10.3390/molecules25092050 -
Bioorganic & Medicinal Chemistry Letters Jun 2020Novel nucleoside analogues named "triazoxins" were synthesized. Of these, two analogues were found to be highly effective against Giardia lamblia, an intestinal parasite...
Novel nucleoside analogues named "triazoxins" were synthesized. Of these, two analogues were found to be highly effective against Giardia lamblia, an intestinal parasite and a major cause of waterborne infection, worldwide. While compound 7 reduced the growth of trophozoites in culture (IC, ~5 μM), compound 21 blocked the in vitro cyst production (IC ~5 μM). Compound 21 was also effective against trophozoites (IC, ~36 μM). A third analogue (compound 8) was effective against both trophozoites (IC, ~36 μM) and cysts (IC, ~20 μM) although at higher concentration. Thus triazoxin analogues are unique and exhibit morphology (i.e., trohozoites or cysts) -specific effects against Giardia.
Topics: Anti-Infective Agents; Catalysis; Drug Design; Giardia lamblia; Giardiasis; Humans; Imidazoles; Molecular Structure; Nucleosides; Propanols; Structure-Activity Relationship; Trophozoites; Uridine
PubMed: 32327222
DOI: 10.1016/j.bmcl.2020.127175 -
Nanoscale Advances Apr 2021Nucleoside and nucleotide analogs are essential tools in our limited arsenal in the fight against cancer. However, these structures face severe drawbacks such as rapid... (Review)
Review
Nucleoside and nucleotide analogs are essential tools in our limited arsenal in the fight against cancer. However, these structures face severe drawbacks such as rapid plasma degradation or hydrophilicity, limiting their clinical application. Here, different aspects of nucleoside and nucleotide analogs have been exposed, while providing their shortcomings. Aiming to improve their fate in the body and combating their drawbacks, two different approaches have been discussed, the prodrug and nanocarrier technologies. Finally, a novel approach called "PUFAylation" based on both the prodrug and nanocarrier technologies has been introduced, promising to be the supreme method to create a novel nucleoside or nucleotide analog based formulation, with enhanced efficacy and highly reduced toxicity.
PubMed: 36133769
DOI: 10.1039/d0na01084g -
International Journal of Dermatology Oct 2017Recently, the unregulated use of untested synthetic alpha-melanocyte-stimulating hormone (α-MSH) analogues, commonly known as melanotan I and II, appears to have... (Review)
Review
Recently, the unregulated use of untested synthetic alpha-melanocyte-stimulating hormone (α-MSH) analogues, commonly known as melanotan I and II, appears to have increased. These analogues are primarily used for their tan-stimulating effects. Dermatologists see many patients in their clinic who tan. This review provides an overview of the risks of the unregulated use of these substances. Other topics discussed here include the history and safety of afamelanotide, which is the only α-MSH analogue that is approved for use in a limited number of medical indications. Although afamelanotide has been thoroughly tested and deemed safe, illegal melanotans are likely risky for several reasons. There are questions regarding the preparation, administration, and dosage of these substances. In addition to these general risks, increasing numbers of case reports indicate that the unregulated use of both melanotan I and II is associated with cutaneous complications, particularly melanocytic changes in existing moles and newly emerging (dysplastic) nevi. Four case reports have described melanomas emerging from existing moles either during or shortly after the use of melanotan. Although conclusive evidence linking these phenomena is lacking, publications have stressed the importance of awareness that melanotan is a part of a 'tanning culture' in certain subpopulations. Multiple national health organizations have issued safety warnings regarding the use of melanotan I and II.
Topics: Dermatologic Agents; Drug Compounding; Humans; Peptides, Cyclic; Risk Factors; Self Medication; alpha-MSH
PubMed: 28266027
DOI: 10.1111/ijd.13585 -
Endocrine-related Cancer Dec 2016Acromegaly is a hormonal disorder that arises when the pituitary gland secretes excess growth hormone (GH), which in turn stimulates a concomitant increase in serum... (Review)
Review
Acromegaly is a hormonal disorder that arises when the pituitary gland secretes excess growth hormone (GH), which in turn stimulates a concomitant increase in serum insulin-like growth factor 1 (IGF-1) levels. Gastroenteropancreatic neuroendocrine tumours (GEP-NET) constitute a heterogeneous group of tumours that can secrete serotonin and a variety of peptide hormones that may cause characteristic symptoms known as carcinoid syndrome or other symptoms and hormonal hypersecretion syndromes depending on the tumour's site of origin. Current medical therapy for the treatment of acromegaly and GEP-NET involves the administration of somatostatin analogues that effectively suppress excess hormone secretion. After its discovery in 1979, octreotide became the first synthetic biologically stable somatostatin analogue with a short-acting formulation of octreotide introduced into clinical practice in the late 1980s. Lanreotide, another somatostatin analogue, became available in the mid-1990s initially as a prolonged-release formulation administered every 10 or 14 days. Long-acting release formulations of both octreotide (Sandostatin LAR and Novartis) and lanreotide (Somatuline Autogel, Ipsen), based on microparticle and nanoparticle drug-delivery technologies, respectively, were later developed, which allowed for once-monthly administration and improved convenience. First-generation somatostatin analogues remain one of the cornerstones of medical therapy in the management of pituitary and GEP-NET hormone hypersecretion, with octreotide having the longest established efficacy and safety profile of the somatostatin analogue class. More recently, pasireotide (Signifor), a next-generation multireceptor-targeted somatostatin analogue, has emerged as an alternative therapeutic option for the treatment of acromegaly. This review summarizes the development and clinical success of somatostatin analogues.
Topics: Acromegaly; Adenoma; Antineoplastic Agents; Growth Hormone-Secreting Pituitary Adenoma; Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Peptides, Cyclic; Somatostatin; Stomach Neoplasms
PubMed: 27697899
DOI: 10.1530/ERC-16-0151 -
The Journal of Biological Chemistry Nov 2021Detection of thymidine analogues after their incorporation into replicating DNA represents a powerful tool for the study of cellular DNA synthesis, progression through... (Review)
Review
Detection of thymidine analogues after their incorporation into replicating DNA represents a powerful tool for the study of cellular DNA synthesis, progression through the cell cycle, cell proliferation kinetics, chronology of cell division, and cell fate determination. Recent advances in the concurrent detection of multiple such analogues offer new avenues for the investigation of unknown features of these vital cellular processes. Combined with quantitative analysis, temporal discrimination of multiple labels enables elucidation of various aspects of stem cell life cycle in situ, such as division modes, differentiation, maintenance, and elimination. Data obtained from such experiments are critically important for creating descriptive models of tissue histogenesis and renewal in embryonic development and adult life. Despite the wide use of thymidine analogues in stem cell research, there are a number of caveats to consider for obtaining valid and reliable labeling results when marking replicating DNA with nucleotide analogues. Therefore, in this review, we describe critical points regarding dosage, delivery, and detection of nucleotide analogues in the context of single and multiple labeling, outline labeling schemes based on pulse-chase, cumulative and multilabel marking of replicating DNA for revealing stem cell proliferative behaviors, and determining cell cycle parameters, and discuss preconditions and pitfalls in conducting such experiments. The information presented in our review is important for rational design of experiments on tracking dividing stem cells by marking replicating DNA with thymidine analogues.
Topics: Animals; Cell Cycle; Cell Self Renewal; Cell Tracking; DNA Replication; Humans; Stem Cells; Thymidine
PubMed: 34717955
DOI: 10.1016/j.jbc.2021.101345 -
BioMed Research International 2020Replacing a single tooth in the anterior maxilla is one of the greatest challenges in dentistry. Both functional and aesthetic results are to be strictly pursued....
Replacing a single tooth in the anterior maxilla is one of the greatest challenges in dentistry. Both functional and aesthetic results are to be strictly pursued. Planning and executing such a case through a totally digital methodology eventually guarantee many advantages, above all patient's operative and postoperative comfort. To ascertain this, a BOP analysis was performed which allowed us to evaluate soft tissues health, and more; crestal bone resorption was measured to evaluate hard tissues stability. This assumption was studied through four cases in which patients were alternatively treated with analogic and digital techniques. Four homogeneous patients were recruited. They all needed to extract one of the upper incisors, due to different clinical reasons, and then to replace it with an implant. Each patient was treated with an immediate postextractive implant which was immediately loaded, and finally, analogical and digital techniques were compared. All patients underwent a preoperative CBCT examination. After surgery, patients were checked by the surgeon after 10 days and one month to evaluate the progress of healing and to exclude any prosthetic problem. At 6 months (T1), one year (T2), and three years (T3), intraoral x-rays were performed using customized centring devices, according to the parallel beam technique. All data have been collected in a table and statistically processed; mean and standard deviation were measured. All patients entered an oral hygiene program with six months recall. Dental hygienist checked the BOP at T1, T2, and T3. At every step, similar levels of BOP were recorded. About interproximal bone loss, all patients showed an initial moderate loss (between T1 and T2), followed by stable values between T2 and T3. Despite the important limitations of a study with few cases, these results show a similar outcome comparing digital and analogical methods.
Topics: Adult; Alveolar Bone Loss; Crowns; Dental Implants, Single-Tooth; Esthetics, Dental; Follow-Up Studies; Humans; Immediate Dental Implant Loading; Incisor; Maxilla; Tooth Extraction; Tooth Socket; Treatment Outcome
PubMed: 33150174
DOI: 10.1155/2020/4012127 -
Pituitary Jun 2016The somatostatin analogues octreotide LAR and lanreotide Autogel have been evaluated for the treatment of acromegaly in numerous clinical trials, with considerable... (Review)
Review
CONTEXT
The somatostatin analogues octreotide LAR and lanreotide Autogel have been evaluated for the treatment of acromegaly in numerous clinical trials, with considerable heterogeneity in reported biochemical response rates. This review examines and attempts to account for these differences in response rates reported in the literature.
EVIDENCE ACQUISITION
PubMed was searched for English-language studies of a minimum duration of 24 weeks that evaluated ≥10 patients with acromegaly treated with octreotide LAR or lanreotide Autogel from 1990 to March 2015 and reported GH and/or IGF-1 data as the primary objective of the study.
EVIDENCE SYNTHESIS
Of the 190 clinical trials found, 18 octreotide LAR and 15 lanreotide Autogel studies fulfilled the criteria for analysis. It is evident from the protocols of these studies that multiple factors are capable of impacting on reported response rates. Prospective studies reporting an intention-to-treat analysis that evaluated medically naïve patients and used the composite endpoint of both GH and IGF-1 control were associated with lower response rates. The use of non-composite biochemical control endpoints, heterogeneous patient populations, analyses that exclude treatment non-responders, assay variability and prior responsiveness to medical therapy are just a few of the factors identified that likely contribute to higher success rates.
CONCLUSIONS
The wide range of reported response rates with somatostatin analogues may be confusing and could lead to misinterpretation by both the patient and the physician in certain situations. Understanding the factors that potentially drive the variation in response rates should allow clinicians to better gauge treatment expectations in specific patients.
Topics: Adenoma; Antineoplastic Agents, Hormonal; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Octreotide; Peptides, Cyclic; Somatostatin; Treatment Outcome
PubMed: 26519143
DOI: 10.1007/s11102-015-0684-z